text:
Charles Maurice de Talleyrand-Périgord

Charles-Maurice de Talleyrand-Périgord (, ; 2 February 1754 – 17 May 1838), 1st Prince of Benevento, then Prince of Talleyrand, was a French secularized clergyman, statesman, and leading diplomat. After studying theology, he became Agent-General of the Clergy in 1780. In 1789, just before the French Revolution, he became Bishop of Autun. He worked at the highest levels of successive French governments, most commonly as foreign minister or in some other diplomatic capacity. His career spanned the regimes of Louis XVI, the years of the French Revolution, Napoleon, Louis XVIII, and Louis Philippe I. Those Talleyrand served often distrusted him but, like Napoleon, found him extremely useful. The name "Talleyrand" has become a byword for crafty and cynical diplomacy.

He was Napoleon's chief diplomat during the years when French military victories brought one European state after another under French hegemony. However, most of the time, Talleyrand worked for peace so as to consolidate France's gains. He succeeded in obtaining peace with Austria through the 1801 Treaty of Lunéville and with Britain in the 1802 Treaty of Amiens. He could not prevent the renewal of war in 1803 but by 1805 he opposed his emperor's renewed wars against Austria, Prussia, and Russia. He resigned as foreign minister in August 1807, but retained the trust of Napoleon. He conspired to undermine the emperor's plans through secret dealings with Tsar Alexander I of Russia and the Austrian minister Klemens von Metternich. Talleyrand sought a negotiated secure peace so as to perpetuate the gains of the French Revolution. Napoleon rejected peace; when he fell in 1814, Talleyrand supported the Bourbon Restoration decided by the Allies. He played a major role at the Congress of Vienna in 1814–1815, where he negotiated a favorable settlement for France and played a role in unwinding the Napoleonic Wars.

Talleyrand polarizes opinion. Some regard him as one of the most versatile, skilled and influential diplomats in European history, while some believe that he was a traitor, betraying in turn the ancien régime, the French Revolution, Napoleon, and the Bourbon Restoration.

Early life
Talleyrand was born in Paris into an aristocratic family which, though ancient and illustrious, was not particularly prosperous. His father, Count Charles Daniel de Talleyrand-Périgord, was 20 years of age when Charles was born. His mother was Alexandrine de Damas d'Antigny. Both his parents held positions at court, but as the youngest children of their respective families, had no important income. Talleyrand's father had a long career in the French Royal Army, reaching the rank of lieutenant general, as did his uncle, Gabriel Marie de Périgord, despite having the same infirmity from which Talleyrand would suffer throughout his life. His father served all through the Seven Years' War.

From childhood, Talleyrand walked with a limp, which caused him to later be called le diable boiteux (French for "the lame devil") among other nicknames. In his Memoirs, he linked this infirmity to an accident at age four, but recent research has shown that his limp was in fact congenital. It might have been a congenital clubfoot. In any case, his handicap made him unable to follow his father into a military career, leaving the obvious career of the Church.

The latter held out the hope for Charles-Maurice of succeeding his uncle, Alexandre Angélique de Talleyrand-Périgord, then Archbishop of Reims, one of the most prestigious and richest dioceses in France. At eight years old, Talleyrand attended the Collège d'Harcourt, the seminary of Saint-Sulpice, while studying theology at the Sorbonne until the age of 21. In his free time, he read the works of Montesquieu, Voltaire, and other writers who were beginning to question the authority of the ancien régime in matters of church and state. As subdeacon he witnessed the coronation of Louis XVI at Reims in 1775.

He was not ordained a priest until four years later, on 19 December 1779, at the age of 25. Very soon, in 1780, he attained the influential position of Agent-General of the Clergy, and was instrumental in promoting the drawing up of a general inventory of Church properties in France as of 1785, along with a defense of "inalienable rights of the Church", the latter being a stance he later denied. In 1788, the influence of Talleyrand's father and family overcame the King's dislike and obtained his appointment as Bishop of Autun, with a stipend of 22,000 livres. He was consecrated a bishop on 4 January 1789 by Louis-André de Grimaldi. The undoubtedly able Talleyrand, though hardly devout and even free-thinking in the Enlightenment mold, was outwardly respectful of religious observance. In the course of the Revolution, however, he was to manifest his cynicism and abandon all orthodox Catholic practice. He resigned his bishopric on 13 April 1791. On 29 June 1802, Pope Pius VII laicized Talleyrand, an event most uncommon at the time in the history of the Church.

French Revolution
Shortly after he was consecrated as Bishop of Autun, Talleyrand attended the Estates-General of 1789, representing the clergy, the First Estate. During the French Revolution, Talleyrand strongly supported the anti-clericalism of the revolutionaries. Along with Mirabeau, he promoted the appropriation of Church properties. He participated in the writing of the Declaration of the Rights of Man and of the Citizen and proposed the Civil Constitution of the Clergy that nationalized the Church in preference to allegiance to the Pope, and swore in the first four constitutional bishops, even though he had himself resigned as Bishop following his excommunication by Pope Pius VI in 1791. During the Fête de la Fédération on 14 July 1790, Talleyrand celebrated Mass. Notably, he promoted public education in full spirit of the Enlightenment by preparing a 216-page Report on Public Instruction. It proposed pyramidical structure rising through local, district, and departmental schools, and parts were later adopted. During his 5-month tenure in the Estates-General, Talleyrand was also involved in drawing up the police regulations of Paris, proposed the suffrage of Jews, supported a ban on the tithes, and invented a method to ensure loans. Few bishops followed him in obedience to the new decree, and much of the French clergy came to view him as schismatic.

Just before his resignation from the bishopric, Talleyrand had been elected, with Mirabeau and the Abbé Sieyès, a member of the department of Paris. In that capacity he did useful work for some eighteen months in seeking to support the cause of order in the turbulent capital. Though he was often on strained terms with Mirabeau, his views generally coincided with those of that statesman, who before he died is said to have advised Talleyrand to develop a close understanding with England.

In 1792, he was sent twice, unofficially, to London to avert war, and he was cordially received by Pitt and Grenville. After his first visit, he persuaded the then foreign minister, Charles François Dumouriez, of the importance of having a fully accredited ambassador in London, and the marquis de Chauvelin was duly appointed, with Talleyrand as his deputy. Still, after an initial British declaration of neutrality during the first campaigns of 1792, his mission ultimately failed. In September 1792, he left Paris for England having acquired a passport from Danton personally just at the beginning of the September massacres. The National Convention issued a warrant for his arrest in December 1792. In March 1794, with the two countries at the brink of war, he was forced to leave Britain by Pitt's expulsion order. He then went to the neutral country of the United States.

The ship he took to the US was forced by rough weather in the Channel to stop at Falmouth where Talleyrand recounts an awkward chance meeting with Benedict Arnold at an inn.

During Talleyrand's stay in the US, he supported himself by working as a bank agent, involved in commodity trading and real estate speculation. He was a house guest of Aaron Burr of New York and collaborated with Theophile Cazenove in Philadelphia. On 19 May 1794 Matthew Clarkson, the mayor of Philadelphia, received his oath. Talleyrand swore "that I will be faithful and bear true allegiance to...the United States of America... " Burr later sought similar refuge in Talleyrand's home during his self-imposed European exile (1808–12). However, Talleyrand would refuse to return the favor because Burr had killed Talleyrand's friend Alexander Hamilton in an 1804 duel. Talleyrand returned to France in 1796.

After 9 Thermidor, he mobilized his friends (most notably the abbé Martial Borye Desrenaudes and Germaine de Staël) to lobby in the National Convention and the newly established Directoire for his return. His name was suppressed from the émigré list and he returned to France on 25 September 1796. After gaining attention by giving addresses on the value of commercial relations with England, and of colonization as a way of renewing the nation, he became Foreign Minister in July 1797. He was behind the demand for bribes in the XYZ Affair which escalated into the Quasi-War, an undeclared naval war with the United States, 1798–1800. Talleyrand saw a possible political career for Napoleon during the Italian campaigns of 1796 to 1797. He wrote many letters to Napoleon, and the two became close allies. Talleyrand was against the destruction of the Republic of Venice, but he complimented Napoleon when the Treaty of Campo Formio with Austria was concluded (Venice was given to Austria), probably because he wanted to reinforce his alliance with Napoleon. Later in 1797, Talleyrand was instrumental in assisting with the Coup of 18 Fructidor, which ousted two moderate members of the Directory in favor of the Jacobins headed by Paul Barras.

Under Napoleon
Talleyrand, along with Napoleon's younger brother, Lucien Bonaparte, was instrumental in the 1799 coup d'état of 18 Brumaire, establishing the French Consulate government, although he also made preparations for flight if necessary. He also persuaded Barras to resign as Director. Talleyrand was soon made Foreign Minister by Napoleon, although he rarely agreed with Napoleon's foreign policy. Domestically, Talleyrand used his influence to help in the repeal of the strict laws against émigrés, refractory clergy, and the royalists of the west. The Pope released him from the ban of excommunication in the Concordat of 1801, which also revoked the Civil Constitution of the Clergy. Talleyrand was instrumental in the completion of the Treaty of Amiens in 1802. He wanted Napoleon to keep peace afterwards, as he thought France had reached its maximum expansion.

Talleyrand was an integral player in the German mediatization. While the Treaty of Campo Formio of 1797 had, on paper, stripped German princes of their lands beyond the left bank of the Rhine, it was not enforced until the Treaty of Lunéville in 1801. As the French annexed these lands, leaders believed that rulers of states such as Baden, Bavaria, Württemberg, Prussia, Hesse and Nassau, who lost territories on the Left Bank, should receive new territories on the Right Bank through the secularization of ecclesiastical principalities. Many of these rulers gave out bribes in order to secure new lands, and Talleyrand and some of his associates amassed about 10 million francs in the process. This was the first blow in the destruction of the Holy Roman Empire.

While helping to establish French supremacy in neighboring states and assisting Bonaparte in securing the title of First Consul for life, Talleyrand sought all means of securing the permanent welfare of France. He worked hard to prevent the rupture of the peace of Amiens which occurred in May 1803, and he did what he could to prevent the Louisiana Purchase earlier in the year. These events, as he saw, told against the best interests of France and endangered the gains which she had secured by war and diplomacy. Thereafter he strove to moderate Napoleon's ambition and to preserve the European system as far as possible.

Napoleon forced Talleyrand into marriage in September 1802 to longtime mistress Catherine Grand (née Worlée). Talleyrand purchased the Château de Valençay in May 1803, upon the urging of Napoleon. This later was used as the site of imprisonment of the Spanish royal family in 1808–1813, after Napoleon's invasion of Spain.

In May 1804, Napoleon bestowed upon Talleyrand the title of Grand Chamberlain of the Empire, with almost 500,000 francs a year. In 1806, he was made Sovereign Prince of Benevento (or Bénévent), a former Papal fief in southern Italy. Talleyrand held the title until 1815 and administered the principality concurrently with his other tasks.

Talleyrand was opposed to the harsh treatment of Austria in the 1805 Treaty of Pressburg and of Prussia in the Peace of Tilsit in 1807. In 1806, after Pressburg, he profited greatly from the reorganization of the German lands, this time into the Confederation of the Rhine. He negotiated the Treaty of Posen with Saxony, but was shut out completely from the negotiations at Tilsit. After Queen Louise of Prussia failed in her appeal to Napoleon to spare her nation, she wept and was consoled by Talleyrand. This gave him a good name among the elites of European nations outside France.

Changing sides

Having wearied of serving a master in whom he no longer had much confidence, Talleyrand resigned as minister of foreign affairs in 1807, although the Emperor retained him in the Council of State as Vice-Grand Elector of the Empire. He disapproved of Napoleon's Spanish initiative, which resulted in the Peninsular War beginning in 1808. At the Congress of Erfurt in September–October 1808, Talleyrand secretly counseled Tsar Alexander. The Tsar's attitude towards Napoleon was one of apprehensive opposition. Talleyrand repaired the confidence of the Russian monarch, who rebuked Napoleon's attempts to form a direct anti-Austrian military alliance. Napoleon had expected Talleyrand to help convince the Tsar to accept his proposals and never discovered that Talleyrand was working at cross-purposes. Talleyrand believed Napoleon would eventually destroy the empire he had worked to build across multiple rulers.

After his resignation in 1807 from the ministry, Talleyrand began to accept bribes from hostile powers (mainly Austria, but also Russia), to betray Napoleon's secrets. Talleyrand and Joseph Fouché, who were typically enemies in both politics and the salons, had a rapprochement in late 1808 and entered into discussions over the imperial line of succession. Napoleon had yet to address this matter and the two men knew that without a legitimate heir a struggle for power would erupt in the wake of Napoleon's death. Even Talleyrand, who believed that Napoleon's policies were leading France to ruin, understood the necessity of peaceful transitions of power. Napoleon received word of their actions and deemed them treasonous. This perception caused the famous dressing down of Talleyrand in front of Napoleon's marshals, during which Napoleon famously claimed that he could "break him like a glass, but it's not worth the trouble" and added with a scatological tone that Talleyrand was "shit in a silk stocking", to which the minister coldly retorted, once Napoleon had left, "Pity that so great a man should have been so badly brought up!"

Talleyrand opposed the further harsh treatment of Austria in 1809 after the War of the Fifth Coalition. He was also a critic of the French invasion of Russia in 1812. He was invited to resume his former office in late 1813, but Talleyrand could see that power was slipping from Napoleon's hands. He offered to resign from the council in early 1814, but Napoleon refused the move. Talleyrand then hosted the tsar at the end of March after the fall of Paris, persuaded him that the best chance of stability lay with the House of Bourbon, and gained his support. On 1 April 1814 he led the Sénat conservateur in establishing a provisional government in Paris, of which he was elected president. On 2 April the Senate officially deposed Napoleon with the Acte de déchéance de l'Empereur; by 11 April it had approved the Treaty of Fontainebleau and adopted a new constitution to re-establish the Bourbon monarchy.

Bourbon Restoration and July Monarchy

When Napoleon was succeeded by Louis XVIII in April 1814, Talleyrand was one of the key agents of the restoration of the House of Bourbon, although he opposed the new legislation of Louis's rule. Talleyrand was the chief French negotiator at the Congress of Vienna; earlier that same year he signed the Treaty of Paris. It was due in part to his skills that the terms of the treaty were remarkably lenient towards France. As the Congress opened, the right to make decisions was restricted to four countries: Austria, the United Kingdom, Prussia and Russia. France and other European countries were invited to attend, but were not allowed to influence the process. Talleyrand promptly became the champion of the small countries and demanded admission into the ranks of the decision-making process. The four powers admitted France and Spain to the decision-making backrooms of the conference after a good deal of diplomatic maneuvering by Talleyrand, who had the support of the Spanish representative, Pedro Gómez Labrador, Marquis of Labrador. Spain was excluded after a while (a result of both the Marquis of Labrador's incompetence as well as the quixotic nature of Spain's agenda), but France (Talleyrand) was allowed to participate until the end. Russia and Prussia sought to enlarge their territory at the Congress. Russia demanded annexation of Poland (already occupied by Russian troops); this demand was finally satisfied, despite protests by France, Austria and the United Kingdom. Austria was afraid of future conflicts with Russia or Prussia and the United Kingdom was opposed to their expansion as well—and Talleyrand managed to take advantage of these contradictions within the former anti-French coalition. On 3 January 1815, a secret treaty was signed by France's Talleyrand, Austria's Metternich and Britain's Castlereagh. By this tract, officially a secret treaty of defensive alliance, the three powers agreed to use force if necessary to "repulse aggression" (of Russia and Prussia) and to protect the "state of security and independence."

Talleyrand, having managed to establish a middle position, received some favors from the other countries in exchange for his support: France returned to its 1792 boundaries without reparations, with French control over the papal Comtat Venaissin, County of Montbéliard, and Salm, which had been independent at the start of the French Revolution in 1789. It would later be debated which outcome would have been better for France: allowing Prussia to annex all of Saxony (Talleyrand ensured that only part of the kingdom would be annexed) or the Rhine provinces. The first option would have kept Prussia farther away from France, but would have needed much more opposition as well. Some historians have argued that Talleyrand's diplomacy wound up establishing the fault lines of World War I, especially as it allowed Prussia to engulf small German states west of the Rhine. This simultaneously placed the Prussian Army at the French-German frontier, for the first time; made Prussia the largest German power in terms of territory, population and the industry of the Ruhr and Rhineland; and eventually helped pave the way to German unification under the Prussian throne. However, at the time Talleyrand's diplomacy was regarded as successful, as it removed the threat of France being partitioned by the victors. Talleyrand also managed to strengthen his own position in France (ultraroyalists had disapproved of the presence of a former "revolutionary" and "murderer of the Duke d'Enghien" in the royal cabinet).

Napoleon's return to France in 1815 and his subsequent defeat, the Hundred Days, was a reverse for the diplomatic victories of Talleyrand (who remained in Vienna the whole time). The second peace settlement was markedly less lenient and it was fortunate for France that the business of the Congress had been concluded. Having been appointed foreign minister and president of the council on 9 July 1815, Talleyrand resigned in September of that year, over his objections to the second treaty. Louis XVIII appointed him as the Grand Chamberlain of France, a mostly ceremonial role which provided Talleyrand with a steady income. For the next fifteen years he restricted himself to the role of "elder statesman", criticizing and intriguing against Minister of Police Élie, duc Decazes, Prime Minister Duc de Richelieu and other political opponents from the sidelines. In celebration of the birth of the Duc de Bordeaux, Louis XVIII made Talleyrand a knight of the Order of the Holy Spirit.

In December 1829, Talleyrand funded the foundation of the National newspaper. The newspaper was run by his personal friend Adolphe Thiers, alongside Armand Carrel, François Mignet and Stendhal. Its first issue appeared on 3 January 1830, quickly becoming the mouthpiece of the Orléanist cause and gaining popularity among the French liberal bourgeoisie. Following the ascent of Louis-Philippe I to the throne in the aftermath of the July Revolution of 1830, Talleyrand reluctantly agreed to become ambassador to the United Kingdom, a post he held from 1830 to 1834. In this role, he strove to reinforce the legitimacy of Louis-Philippe's regime. He played a vital role in the London Conference of 1830, rebuking a partition plan developed by his son Charles de Flahaut and helping bring Leopold of Saxe-Coburg to the throne of the newly independent Kingdom of Belgium. In April 1834 he crowned his diplomatic career by signing the treaty which brought together as allies France, Great Britain, Spain and Portugal.

After resigning from his position as ambassador in London in November 1834, Talleyrand stopped playing an active role in French politics. He split his time between Château de Valençay and Saint-Florentin, where he hosted frequent banquets and played whist with his visitors. His physical health began to steadily deteriorate and he began using an armchair on wheels provided to him by Louis Philippe I. He spent most of his time in the company of the Duchess Dino and concerned himself with the education of her daughter Pauline. Talleyrand suffered from bouts of recurring depression which were caused by his concern over his legacy and the development of the Napoleonic myth. To that end he ordered that his autobiography, the Memoirs, be published 30 years after his death. He also sought to gain the friendship of people he believed would shape public opinion in the future, including Honoré de Balzac, Lady Granville and Alphonse de Lamartine. During the last years of his life Talleyrand began planning his reconciliation with the Catholic Church. On 16 May 1838, he signed a retraction of his errors towards the church and a letter of submission to Pope Gregory XVI. He died the following day at 3:55 p.m., at Saint-Florentin.

By a codicil added to his will on 17 March 1838, Talleyrand left his memoirs and papers to the duchess of Dino and Adolphe de Bacourt. The latter revised them with care, and added to them other pieces emanating from Talleyrand. They fell into some question: first that Talleyrand is known to have destroyed many of his most important papers, and secondly that de Bacourt almost certainly drew up the connected narrative which we now possess from notes which were in more or less of confusion. The mémoires were later edited by the duc de Broglie and published in 1891.

Private life

Talleyrand had a reputation for Promiscuity and as a voluptuary. He left no legitimate children, though he possibly fathered over two dozen illegitimate ones. Four possible children of his have been identified: Charles Joseph, comte de Flahaut, generally accepted to be an illegitimate son of Talleyrand; the painter Eugène Delacroix, once rumoured to be Talleyrand's son, though this is doubted by historians who have examined the issue (for example, Léon Noël, French ambassador); the "Mysterious Charlotte", possibly his daughter by his future wife, Catherine Worlée Grand; and Pauline, ostensibly the daughter of the Duke and Duchess Dino. Of these four, only the first is given credence by historians. However, the French historian Emmanuel de Waresquiel has lately given much credibility to father-daughter link between Talleyrand and Pauline whom he referred to as "my dear Minette". Thaddeus Stevens "suffered too from the rumor that he was actually the bastard son of Count Talleyrand, who was said to have visited New England in the year before Stevens' birth.... Actually Talleyrand did not visit New England till 1794, when Stevens was already two years old."

Aristocratic women were a key component of Talleyrand's political tactics, both for their influence and their ability to cross borders unhindered. His presumed lover Germaine de Staël was a major influence on him, and he on her. Though their personal philosophies were most different (she a romantic, he very much unsentimental), she assisted him greatly, most notably by lobbying Barras to permit Talleyrand to return to France from his American exile, and then to have him made foreign minister. He lived with Catherine Worlée, born in India and married there to Charles Grand. She had traveled about before settling in Paris in the 1780s, where she lived as a notorious courtesan for several years before divorcing Grand to marry Talleyrand. Talleyrand was in no hurry to marry, and it was after repeated postponements that Napoleon obliged him in 1802 to formalize the relationship or risk his political career. While serving as a high level negotiator at the Congress of Vienna (1814–1815), Talleyrand entered into an arrangement with Dorothea von Biron, the wife of his nephew, the Duke of Dino. Shortly after, he separated from Catherine.

Talleyrand's venality was notorious; in the tradition of the ancien régime, he expected to be paid for the state duties he performed—whether these can properly be called "bribes" is open to debate. For example, during the German mediatization, the consolidation of the small German states, a number of German rulers and elites paid him to save their possessions or enlarge their territories. Less successfully, he solicited payments from the United States government to open negotiations, precipitating a diplomatic disaster (the "XYZ Affair"). The difference between his diplomatic success in Europe and failure with the United States illustrates that his diplomacy rested firmly on the power of the French army that was a terrible threat to the German states within reach, but lacked the logistics to threaten the US not the least because of the British naval domination of the seas. After Napoleon's defeat, he withdrew claims to the title "Prince of Benevento", but was created Duke of Talleyrand with the style "Prince de Talleyrand" for life, in the same manner as his estranged wife.

Described by biographer Philip Ziegler as a "pattern of subtlety and finesse" and a "creature of grandeur and guile", Talleyrand was a great conversationalist, gourmet, and wine connoisseur. He was a frequent visitor at the salon hosted by Adèle de Bellegarde and her sister Aurore, with whom he dined regularly over a period of five years. From 1801 to 1804, he owned Château Haut-Brion in Bordeaux. In 1803, Napoleon ordered Talleyrand to acquire the Château de Valençay as a place particularly appropriate for reception of foreign dignitaries, and Talleyrand made it his primary place of residence until his death in 1838. There he employed the renowned French chef Marie-Antoine Carême, one of the first celebrity chefs known as the "chef of kings and king of chefs", and was said to have spent an hour every day with him. His Paris residence on the Place de la Concorde, acquired in 1812 and sold to James Mayer de Rothschild in 1838, is now owned by the Embassy of the United States.

Talleyrand has been regarded as a traitor because of his support for successive regimes, some of which were mutually hostile. According to French philosopher Simone Weil, criticism of his loyalty is unfounded, as Talleyrand served not every regime as had been said, but in reality "France behind every regime".

Near the end of his life, Talleyrand became interested in Catholicism again while teaching his young granddaughter simple prayers. The Abbé Félix Dupanloup came to Talleyrand in his last hours, and according to his account Talleyrand made confession and received extreme unction. When the abbé tried to anoint Talleyrand's palms, as prescribed by the rite, he turned his hands over to make the priest anoint him on the back of the hands, since he was a bishop. He also signed, in the abbé's presence, a solemn declaration in which he openly disavowed "the great errors which … had troubled and afflicted the Catholic, Apostolic and Roman Church, and in which he himself had had the misfortune to fall." He died on 17 May 1838 and was buried in the Notre-Dame Chapel, near his Château de Valençay.

Today, when speaking of the art of diplomacy, the phrase "they are a Talleyrand" is variously used to describe a statesman of great resourcefulness and craft, or a cynical and conscienceless self-serving politician.

Honors

 * Pair de France.
 * Knight Grand Cross in the Legion of Honour
 * Knight of the Order of the Holy Spirit
 * Knight of the Order of the Golden Fleece of Spain
 * Knight Grand Cross of the Order of St. Stephen of Hungary.
 * Knight Grand Cross of the Order of Saint Andrew.
 * Knight Grand Cross of the Order of the Red Eagle.
 * Knight Grand Cross of the Order of the Black Eagle.
 * Knight of the Order of the Elephant.
 * Knight of the Order of Saint Hubert.
 * Knight Grand Cross of the Order of the Sun.
 * Knight Grand Cross of the Order of the Crown of Saxony.
 * Member of the American Philosophical Society (elected 1796).

Anecdotes

 * In 1797 a rumor spread that King George III of Great Britain had died. A banker, hoping to make a profit from inside information, appeared at Talleyrand's door seeking information. Talleyrand replied along the lines of, "But of course. I shall be delighted, if the information I have to give be of any use to you." The banker listened with bated breath as Talleyrand continued: "Some say the King of England is dead; others, that he is not dead: for my own part, I believe neither the one nor the other. I tell you this in confidence, but I rely on your discretion."
 * The Spanish ambassador complained to Talleyrand that the seals on his diplomatic letters had been broken. Talleyrand replied, "I shall wager I can guess how the thing happened. I am convinced your despatch was opened by some one who desired to know what was inside."
 * Germaine de Staël's novel Delphine allegedly depicted Talleyrand as an old woman, and herself as the heroine. Upon meeting Madame de Staël, Talleyrand remarked, "They tell me that we are both of us in your novel, in the disguise of women."
 * Talleyrand had a morbid dread of falling out of bed in his sleep. To prevent this, he had his mattresses made with a depression in the center. As a further safety measure, he wore fourteen cotton nightcaps at once, held together by 'a sort of tiara'.
 * Following the arrival of the Allies, Talleyrand's mansion hosted Tsar Alexander. Later, his bedroom became the center of government in the provisional government. It was actually quite common to hold important occurrences in one's bedroom as it was warm for the host while the attendants had to stand in the cold night air.
 * On hearing of the death of a Turkish ambassador, Talleyrand is supposed to have said: "I wonder what he meant by that?" More commonly, the quote is attributed to Metternich, the Austrian diplomat, upon Talleyrand's death in 1838.
 * During the occupation of Paris by the Allies, Prussian General Blücher wanted to destroy the Pont d'Iéna, which was named after a French victory against Prussia. The Prefect of Paris tried everything to change the mind of Blücher, without success, and finally went to Talleyrand asking him whether he could write a letter to the General asking him not to destroy the bridge. Talleyrand instead wrote to Tsar Alexander, who was in person in Paris, asking him to grant to the people of Paris the favor of inaugurating himself the bridge under a new name (Pont de l'École militaire). The Tsar accepted, and Blücher could not then destroy a bridge inaugurated by an ally. The name of the bridge was reverted to its original name under Louis-Philippe.
 * A district of Levenshulme in Manchester, England, is called Talleyrand. There is a local tradition that he stayed there, presumably in 1792–94.

Biographies

 * Brinton, Crane. Lives of Talleyrand (1936), 300 pp scholarly study online
 * Kurtz, Harold. (1958) "Talleyrand (part I)" History Today (Nov 1958) 8#11 pp 741–750. and Part II, (Dec 1958) 8#12 pp 847–871.
 * , popular biography online review
 * Madelin, Louis. Talleyrand (1948), a scholarly biography. online
 * Orieux, Jean. Talleyrand: The Art of Survival (1974) 677pp; scholarly biography
 * Pflaum, Rosalynd. Talleyrand and His World (2010) 478pp, popular biography
 * Orieux, Jean. Talleyrand: The Art of Survival (1974) 677pp; scholarly biography
 * Pflaum, Rosalynd. Talleyrand and His World (2010) 478pp, popular biography

Scholarly studies

 * Blinn, Harold E. "New Light on Talleyrand at the Congress of Vienna." Pacific Historical Review 4#2 1935, pp. 143–160. online
 * Earl, John L. "Talleyrand in Philadelphia, 1794–1796." Pennsylvania Magazine of History and Biography 91#3, 1967, pp. 282–298. online
 * Ferraro, Guglielmo. The Reconstruction of Europe: Talleyrand and the Congress of Vienna, 1814–1815 (1941) online
 * Neave, G. "Monsieur de Talleyrand-Périgord's Qualities" Higher Education Policy 19, 401–409 (2006). online
 * Norman, Barbara. Napoleon and Talleyrand: The last two weeks (1976) online
 * Ross, Steven T. European Diplomatic History, 1789–1815: France Against Europe (1969)
 * Sked, Alan. "Talleyrand and England, 1792–1838: A Reinterpretation", Diplomacy & Statecraft (2006) 17#4 pp. 647–64.
 * Stinchcombe, William. "Talleyrand and the American Negotiations of 1797–1798." Journal of American History 62#3 1975, pp. 575–590. online
 * Swain, J. E. "Talleyrand's Last Diplomatic Encounter." The Historian 1#1 1938, pp. 33–53. online, ambassador to Britain
 * Swain, J. E. "Talleyrand's Last Diplomatic Encounter." The Historian 1#1 1938, pp. 33–53. online, ambassador to Britain

Historiography

 * Moncure, James A. ed. Research Guide to European Historical Biography: 1450–Present (4 vol 1992); 4:1823–33

title: Charles Maurice de Talleyrand-Périgord


text:
User talk:Arab~enwiki

Comment
You wrote in a comment to RK:

 * Just out of curiosity, do you think there is any basis at all for anti-semitism? I mean Shakespeare's [Merchant of Venice]? paints an ugly picture of what a jew will willingly do and it points to avarice, a sin. Plus, there was a news report that all the suicide bombers actually bought all their ammunition and explosives from Isreali's. Just wondering.

while in the Talk page for Palestinians, you claimed that in March 2002 "all Arab members of Knesset were arrested."

The last two assertions are false (they are also ridiculous, but that is besides the point). I would like to see any basis whatsoever for them. The first--hinting that there is a basis for anti-Semitism because Shakespeare portrayed a Jew negatively is beyond ridiculous. It is anti-Semitic. Whatever your feelings on the Arab-Israeli conflict, please do not let it backslide into racist rhetoric. If it already has, I don't think Wikipedia is the place for it. Danny

The question is whether anti-semitism has any basis. Well, I am Jewish and I am greedy. Does this mean (a) that all Jews are greedy or (b) that greedy people should be shunned, etc.?

The other point, about buying arms from Israeli's. Maybe they did that on purpose just to use as "evidence" of Israeli avarice. Who knows? And who cares?

There is really only one issue: are the Israeli goverment's actions sufficiently "bad" to justify killing random civilians? Some (generally Arabs) say yes; some (mostly Jews) say no.

I'd like to see the 'pedia carefully adhere to the NPOV, and say things like
 * many Israel Jews, notably Mr. A, say B
 * some Arabs, such as Mr. C, have said D
 * other Arabs, such as Mr. E, have said F

It is my considered opinion that "Arab" is a troll. Comments such as the above have more the flavor a stereotypical or satirical "Arab" viewpoint than actual ones as recorded daily in press, Internet, and official sources. I believe this person is only trying to stir up trouble, and possibly anti-Arab feeling. I ask that he/she/it not be encouraged. -- April

Stupid Arab! --GorillazFanAdam 03:54, 15 March 2006 (UTC)

Your account will be renamed
Hello,

The developer team at Wikimedia is making some changes to how accounts work, as part of our on-going efforts to provide new and better tools for our users like cross-wiki notifications. These changes will mean you have the same account name everywhere. This will let us give you new features that will help you edit and discuss better, and allow more flexible user permissions for tools. One of the side-effects of this is that user accounts will now have to be unique across all 900 Wikimedia wikis. See the announcement for more information.

Unfortunately, your account clashes with another account also called Arab. To make sure that both of you can use all Wikimedia projects in future, we have reserved the name Arab~enwiki that only you will have. If you like it, you don't have to do anything. If you do not like it, you can pick out a different name. If you think you might own all of the accounts with this name and this message is in error, please visit Special:MergeAccount to check and attach all of your accounts to prevent them from being renamed.

Your account will still work as before, and you will be credited for all your edits made so far, but you will have to use the new account name when you log in.

Sorry for the inconvenience.

Yours, Keegan Peterzell Community Liaison, Wikimedia Foundation 22:05, 19 March 2015 (UTC)

Renamed
 This account has been renamed as part of single-user login finalisation. If you own this account you can |log in using your previous username and password for more information. If you do not like this account's new name, you can choose your own using this form after logging in: . -- Keegan (WMF) (talk) 10:35, 22 April 2015 (UTC)

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: User talk:Arab~enwiki


text:
Dopamine

Dopamine (DA, a contraction of 3,4- d ihydr o xy p henethyl amine ) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% of the catecholamine content in the brain. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical, L-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons (nerve cells) to send signals to other nerve cells. Neurotransmitters are synthesized in specific regions of the brain, but affect many regions systemically. The brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, and many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.

In popular culture and media, dopamine is often portrayed as the main chemical of pleasure, but the current opinion in pharmacology is that dopamine instead confers motivational salience; in other words, dopamine signals the perceived motivational prominence (i.e., the desirability or aversiveness) of an outcome, which in turn propels the organism's behavior toward or away from achieving that outcome.

Outside the central nervous system, dopamine functions primarily as a local paracrine messenger. In blood vessels, it inhibits norepinephrine release and acts as a vasodilator; in the kidneys, it increases sodium excretion and urine output; in the pancreas, it reduces insulin production; in the digestive system, it reduces gastrointestinal motility and protects intestinal mucosa; and in the immune system, it reduces the activity of lymphocytes. With the exception of the blood vessels, dopamine in each of these peripheral systems is synthesized locally and exerts its effects near the cells that release it.

Several important diseases of the nervous system are associated with dysfunctions of the dopamine system, and some of the key medications used to treat them work by altering the effects of dopamine. Parkinson's disease, a degenerative condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra. Its metabolic precursor L-DOPA can be manufactured; Levodopa, a pure form of L-DOPA, is the most widely used treatment for Parkinson's. There is evidence that schizophrenia involves altered levels of dopamine activity, and most antipsychotic drugs used to treat this are dopamine antagonists which reduce dopamine activity. Similar dopamine antagonist drugs are also some of the most effective anti-nausea agents. Restless legs syndrome and attention deficit hyperactivity disorder (ADHD) are associated with decreased dopamine activity. Dopaminergic stimulants can be addictive in high doses, but some are used at lower doses to treat ADHD. Dopamine itself is available as a manufactured medication for intravenous injection. It is useful in the treatment of severe heart failure or cardiogenic shock. In newborn babies it may be used for hypotension and septic shock.

Structure
A dopamine molecule consists of a catechol structure (a benzene ring with two hydroxyl side groups) with one amine group       attached via an ethyl chain. As such, dopamine is the simplest possible catecholamine, a family that also includes the neurotransmitters norepinephrine and epinephrine. The presence of a benzene ring with this amine attachment makes it a substituted phenethylamine, a family that includes numerous psychoactive drugs.

Like most amines, dopamine is an organic base. As a base, it is generally protonated in acidic environments (in an acid-base reaction). The protonated form is highly water-soluble and relatively stable, but can become oxidized if exposed to oxygen or other oxidants. In basic environments, dopamine is not protonated. In this free base form, it is less water-soluble and also more highly reactive. Because of the increased stability and water-solubility of the protonated form, dopamine is supplied for chemical or pharmaceutical use as dopamine hydrochloride—that is, the hydrochloride salt that is created when dopamine is combined with hydrochloric acid. In dry form, dopamine hydrochloride is a fine powder which is white to yellow in color.

Synthesis
Dopamine is synthesized in a restricted set of cell types, mainly neurons and cells in the medulla of the adrenal glands. The primary and minor metabolic pathways respectively are:

 * Primary: L -Phenylalanine → L -Tyrosine → L -DOPA → Dopamine
 * Minor: L -Phenylalanine → L -Tyrosine → p-Tyramine → Dopamine
 * Minor: L -Phenylalanine → m-Tyrosine → m-Tyramine → Dopamine

The direct precursor of dopamine, L -DOPA, can be synthesized indirectly from the essential amino acid phenylalanine or directly from the non-essential amino acid tyrosine. These amino acids are found in nearly every protein and so are readily available in food, with tyrosine being the most common. Although dopamine is also found in many types of food, it is incapable of crossing the blood–brain barrier that surrounds and protects the brain. It must therefore be synthesized inside the brain to perform its neuronal activity.

L -Phenylalanine is converted into L -tyrosine by the enzyme phenylalanine hydroxylase, with molecular oxygen (O2) and tetrahydrobiopterin as cofactors. L -Tyrosine is converted into L -DOPA by the enzyme tyrosine hydroxylase, with tetrahydrobiopterin, O2, and iron (Fe2+) as cofactors. L -DOPA is converted into dopamine by the enzyme aromatic L -amino acid decarboxylase (also known as DOPA decarboxylase), with pyridoxal phosphate as the cofactor.

Dopamine itself is used as precursor in the synthesis of the neurotransmitters norepinephrine and epinephrine. Dopamine is converted into norepinephrine by the enzyme dopamine β-hydroxylase, with O2 and L -ascorbic acid as cofactors. Norepinephrine is converted into epinephrine by the enzyme phenylethanolamine N-methyltransferase with S-adenosyl- L -methionine as the cofactor.

Some of the cofactors also require their own synthesis. Deficiency in any required amino acid or cofactor can impair the synthesis of dopamine, norepinephrine, and epinephrine.

Degradation
Dopamine is broken down into inactive metabolites by a set of enzymes—monoamine oxidase (MAO), catechol-O-methyl transferase (COMT), and aldehyde dehydrogenase (ALDH), acting in sequence. Both isoforms of monoamine oxidase, MAO-A and MAO-B, effectively metabolize dopamine. Different breakdown pathways exist but the main end-product is homovanillic acid (HVA), which has no known biological activity. From the bloodstream, homovanillic acid is filtered out by the kidneys and then excreted in the urine. The two primary metabolic routes that convert dopamine into HVA are:
 * Dopamine → DOPAL → DOPAC → HVA – catalyzed by MAO, ALDH, and COMT respectively
 * Dopamine → 3-Methoxytyramine → HVA – catalyzed by COMT and MAO+ALDH respectively

In clinical research on schizophrenia, measurements of homovanillic acid in plasma have been used to estimate levels of dopamine activity in the brain. A difficulty in this approach however, is separating the high level of plasma homovanillic acid contributed by the metabolism of norepinephrine.

Although dopamine is normally broken down by an oxidoreductase enzyme, it is also susceptible to oxidation by direct reaction with oxygen, yielding quinones plus various free radicals as products. The rate of oxidation can be increased by the presence of ferric iron or other factors. Quinones and free radicals produced by autoxidation of dopamine can poison cells, and there is evidence that this mechanism may contribute to the cell loss that occurs in Parkinson's disease and other conditions.

Cellular effects
Dopamine exerts its effects by binding to and activating cell surface receptors. In humans, dopamine has a high binding affinity at dopamine receptors and human trace amine-associated receptor 1 (hTAAR1). In mammals, five subtypes of dopamine receptors have been identified, labeled from D1 to D5. All of them function as metabotropic, G protein-coupled receptors, meaning that they exert their effects via a complex second messenger system. These receptors can be divided into two families, known as D1-like and D2-like. For receptors located on neurons in the nervous system, the ultimate effect of D1-like activation (D1 and D5) can be excitation (via opening of sodium channels) or inhibition (via opening of potassium channels); the ultimate effect of D2-like activation (D2, D3, and D4) is usually inhibition of the target neuron. Consequently, it is incorrect to describe dopamine itself as either excitatory or inhibitory: its effect on a target neuron depends on which types of receptors are present on the membrane of that neuron and on the internal responses of that neuron to the second messenger cAMP. D1 receptors are the most numerous dopamine receptors in the human nervous system; D2 receptors are next; D3, D4, and D5 receptors are present at significantly lower levels.

Storage, release, and reuptake
Inside the brain, dopamine functions as a neurotransmitter and neuromodulator, and is controlled by a set of mechanisms common to all monoamine neurotransmitters. After synthesis, dopamine is transported from the cytosol into synaptic vesicles by a solute carrier—a vesicular monoamine transporter, VMAT2. Dopamine is stored in these vesicles until it is ejected into the synaptic cleft. In most cases, the release of dopamine occurs through a process called exocytosis which is caused by action potentials, but it can also be caused by the activity of an intracellular trace amine-associated receptor, TAAR1. TAAR1 is a high-affinity receptor for dopamine, trace amines, and certain substituted amphetamines that is located along membranes in the intracellular milieu of the presynaptic cell; activation of the receptor can regulate dopamine signaling by inducing dopamine reuptake inhibition and efflux as well as by inhibiting neuronal firing through a diverse set of mechanisms.

Once in the synapse, dopamine binds to and activates dopamine receptors. These can be postsynaptic dopamine receptors, which are located on dendrites (the postsynaptic neuron), or presynaptic autoreceptors (e.g., the D2sh and presynaptic D3 receptors), which are located on the membrane of an axon terminal (the presynaptic neuron). After the postsynaptic neuron elicits an action potential, dopamine molecules quickly become unbound from their receptors. They are then absorbed back into the presynaptic cell, via reuptake mediated either by the dopamine transporter or by the plasma membrane monoamine transporter. Once back in the cytosol, dopamine can either be broken down by a monoamine oxidase or repackaged into vesicles by VMAT2, making it available for future release.

In the brain the level of extracellular dopamine is modulated by two mechanisms: phasic and tonic transmission. Phasic dopamine release, like most neurotransmitter release in the nervous system, is driven directly by action potentials in the dopamine-containing cells. Tonic dopamine transmission occurs when small amounts of dopamine are released without being preceded by presynaptic action potentials. Tonic transmission is regulated by a variety of factors, including the activity of other neurons and neurotransmitter reuptake.

Central nervous system

Inside the brain, dopamine plays important roles in executive functions, motor control, motivation, arousal, reinforcement, and reward, as well as lower-level functions including lactation, sexual gratification, and nausea. The dopaminergic cell groups and pathways make up the dopamine system which is neuromodulatory.

Dopaminergic neurons (dopamine-producing nerve cells) are comparatively few in number—a total of around 400,000 in the human brain —and their cell bodies are confined in groups to a few relatively small brain areas. However their axons project to many other brain areas, and they exert powerful effects on their targets. These dopaminergic cell groups were first mapped in 1964 by Annica Dahlström and Kjell Fuxe, who assigned them labels starting with the letter "A" (for "aminergic"). In their scheme, areas A1 through A7 contain the neurotransmitter norepinephrine, whereas A8 through A14 contain dopamine. The dopaminergic areas they identified are the substantia nigra (groups 8 and 9); the ventral tegmental area (group 10); the posterior hypothalamus (group 11); the arcuate nucleus (group 12); the zona incerta (group 13) and the periventricular nucleus (group 14).

The substantia nigra is a small midbrain area that forms a component of the basal ganglia. This has two parts—an input area called the pars reticulata and an output area called the pars compacta. The dopaminergic neurons are found mainly in the pars compacta (cell group A8) and nearby (group A9). In humans, the projection of dopaminergic neurons from the substantia nigra pars compacta to the dorsal striatum, termed the nigrostriatal pathway, plays a significant role in the control of motor function and in learning new motor skills. These neurons are especially vulnerable to damage, and when a large number of them die, the result is a parkinsonian syndrome.

The ventral tegmental area (VTA) is another midbrain area. The most prominent group of VTA dopaminergic neurons projects to the prefrontal cortex via the mesocortical pathway and another smaller group projects to the nucleus accumbens via the mesolimbic pathway. Together, these two pathways are collectively termed the mesocorticolimbic projection. The VTA also sends dopaminergic projections to the amygdala, cingulate gyrus, hippocampus, and olfactory bulb. Mesocorticolimbic neurons play a central role in reward and other aspects of motivation. Accumulating literature shows that dopamine also plays a crucial role in aversive learning through its effects on a number of brain regions.

The posterior hypothalamus has dopamine neurons that project to the spinal cord, but their function is not well established. There is some evidence that pathology in this area plays a role in restless legs syndrome, a condition in which people have difficulty sleeping due to an overwhelming compulsion to constantly move parts of the body, especially the legs.

The arcuate nucleus and the periventricular nucleus of the hypothalamus have dopamine neurons that form an important projection—the tuberoinfundibular pathway which goes to the pituitary gland, where it influences the secretion of the hormone prolactin. Dopamine is the primary neuroendocrine inhibitor of the secretion of prolactin from the anterior pituitary gland. Dopamine produced by neurons in the arcuate nucleus is secreted into the hypophyseal portal system of the median eminence, which supplies the pituitary gland. The prolactin cells that produce prolactin, in the absence of dopamine, secrete prolactin continuously; dopamine inhibits this secretion.

The zona incerta, grouped between the arcuate and periventricular nuclei, projects to several areas of the hypothalamus, and participates in the control of gonadotropin-releasing hormone, which is necessary to activate the development of the male and female reproductive systems, following puberty.

An additional group of dopamine-secreting neurons is found in the retina of the eye. These neurons are amacrine cells, meaning that they have no axons. They release dopamine into the extracellular medium, and are specifically active during daylight hours, becoming silent at night. This retinal dopamine acts to enhance the activity of cone cells in the retina while suppressing rod cells—the result is to increase sensitivity to color and contrast during bright light conditions, at the cost of reduced sensitivity when the light is dim.

Basal ganglia

The largest and most important sources of dopamine in the vertebrate brain are the substantia nigra and ventral tegmental area. Both structures are components of the midbrain, closely related to each other and functionally similar in many respects. The largest component of the basal ganglia is the striatum. The substantia nigra sends a dopaminergic projection to the dorsal striatum, while the ventral tegmental area sends a similar type of dopaminergic projection to the ventral striatum.

Progress in understanding the functions of the basal ganglia has been slow. The most popular hypotheses, broadly stated, propose that the basal ganglia play a central role in action selection. The action selection theory in its simplest form proposes that when a person or animal is in a situation where several behaviors are possible, activity in the basal ganglia determines which of them is executed, by releasing that response from inhibition while continuing to inhibit other motor systems that if activated would generate competing behaviors. Thus the basal ganglia, in this concept, are responsible for initiating behaviors, but not for determining the details of how they are carried out. In other words, they essentially form a decision-making system.

The basal ganglia can be divided into several sectors, and each is involved in controlling particular types of actions. The ventral sector of the basal ganglia (containing the ventral striatum and ventral tegmental area) operates at the highest level of the hierarchy, selecting actions at the whole-organism level. The dorsal sectors (containing the dorsal striatum and substantia nigra) operate at lower levels, selecting the specific muscles and movements that are used to implement a given behavior pattern.

Dopamine contributes to the action selection process in at least two important ways. First, it sets the "threshold" for initiating actions. The higher the level of dopamine activity, the lower the impetus required to evoke a given behavior. As a consequence, high levels of dopamine lead to high levels of motor activity and impulsive behavior; low levels of dopamine lead to torpor and slowed reactions. Parkinson's disease, in which dopamine levels in the substantia nigra circuit are greatly reduced, is characterized by stiffness and difficulty initiating movement—however, when people with the disease are confronted with strong stimuli such as a serious threat, their reactions can be as vigorous as those of a healthy person. In the opposite direction, drugs that increase dopamine release, such as cocaine or amphetamine, can produce heightened levels of activity, including, at the extreme, psychomotor agitation and stereotyped movements.

The second important effect of dopamine is as a "teaching" signal. When an action is followed by an increase in dopamine activity, the basal ganglia circuit is altered in a way that makes the same response easier to evoke when similar situations arise in the future. This is a form of operant conditioning, in which dopamine plays the role of a reward signal.

Reward
In the language used to discuss the reward system, reward is the attractive and motivational property of a stimulus that induces appetitive behavior (also known as approach behavior) and consummatory behavior. A rewarding stimulus is one that can induce the organism to approach it and choose to consume it. Pleasure, learning (e.g., classical and operant conditioning), and approach behavior are the three main functions of reward. As an aspect of reward, pleasure provides a definition of reward; however, while all pleasurable stimuli are rewarding, not all rewarding stimuli are pleasurable (e.g., extrinsic rewards like money). The motivational or desirable aspect of rewarding stimuli is reflected by the approach behavior that they induce, whereas the pleasure from intrinsic rewards results from consuming them after acquiring them. A neuropsychological model which distinguishes these two components of an intrinsically rewarding stimulus is the incentive salience model, where "wanting" or desire (less commonly, "seeking" ) corresponds to appetitive or approach behavior while "liking" or pleasure corresponds to consummatory behavior. In human drug addicts, "wanting" becomes dissociated with "liking" as the desire to use an addictive drug increases, while the pleasure obtained from consuming it decreases due to drug tolerance.

Within the brain, dopamine functions partly as a global reward signal. An initial dopamine response to a rewarding stimulus encodes information about the salience, value, and context of a reward. In the context of reward-related learning, dopamine also functions as a reward prediction error signal, that is, the degree to which the value of a reward is unexpected. According to this hypothesis proposed by Montague, Dayan, and Sejnowski, rewards that are expected do not produce a second phasic dopamine response in certain dopaminergic cells, but rewards that are unexpected, or greater than expected, produce a short-lasting increase in synaptic dopamine, whereas the omission of an expected reward actually causes dopamine release to drop below its background level. The "prediction error" hypothesis has drawn particular interest from computational neuroscientists, because an influential computational-learning method known as temporal difference learning makes heavy use of a signal that encodes prediction error. This confluence of theory and data has led to a fertile interaction between neuroscientists and computer scientists interested in machine learning.

Evidence from microelectrode recordings from the brains of animals shows that dopamine neurons in the ventral tegmental area (VTA) and substantia nigra are strongly activated by a wide variety of rewarding events. These reward-responsive dopamine neurons in the VTA and substantia nigra are crucial for reward-related cognition and serve as the central component of the reward system. The function of dopamine varies in each axonal projection from the VTA and substantia nigra; for example, the VTA–nucleus accumbens shell projection assigns incentive salience ("want") to rewarding stimuli and its associated cues, the VTA–prefrontal cortex projection updates the value of different goals in accordance with their incentive salience, the VTA–amygdala and VTA–hippocampus projections mediate the consolidation of reward-related memories, and both the VTA–nucleus accumbens core and substantia nigra–dorsal striatum pathways are involved in learning motor responses that facilitate the acquisition of rewarding stimuli. Some activity within the VTA dopaminergic projections appears to be associated with reward prediction as well.

Pleasure
While dopamine has a central role in causing "wanting," associated with the appetitive or approach behavioral responses to rewarding stimuli, detailed studies have shown that dopamine cannot simply be equated with hedonic "liking" or pleasure, as reflected in the consummatory behavioral response. Dopamine neurotransmission is involved in some but not all aspects of pleasure-related cognition, since pleasure centers have been identified both within the dopamine system (i.e., nucleus accumbens shell) and outside the dopamine system (i.e., ventral pallidum and parabrachial nucleus). For example, direct electrical stimulation of dopamine pathways, using electrodes implanted in the brain, is experienced as pleasurable, and many types of animals are willing to work to obtain it. Antipsychotic drugs reduce dopamine levels and tend to cause anhedonia, a diminished ability to experience pleasure. Many types of pleasurable experiences—such as sexual intercourse, eating, and playing video games—increase dopamine release. All addictive drugs directly or indirectly affect dopamine neurotransmission in the nucleus accumbens; these drugs increase drug "wanting", leading to compulsive drug use, when repeatedly taken in high doses, presumably through the sensitization of incentive-salience. Drugs that increase synaptic dopamine concentrations include psychostimulants such as methamphetamine and cocaine. These produce increases in "wanting" behaviors, but do not greatly alter expressions of pleasure or change levels of satiation. However, opiate drugs such as heroin and morphine produce increases in expressions of "liking" and "wanting" behaviors. Moreover, animals in which the ventral tegmental dopamine system has been rendered inactive do not seek food, and will starve to death if left to themselves, but if food is placed in their mouths they will consume it and show expressions indicative of pleasure.

A clinical study from January 2019 that assessed the effect of a dopamine precursor (levodopa), dopamine antagonist (risperidone), and a placebo on reward responses to music – including the degree of pleasure experienced during musical chills, as measured by changes in electrodermal activity as well as subjective ratings – found that the manipulation of dopamine neurotransmission bidirectionally regulates pleasure cognition (specifically, the hedonic impact of music) in human subjects. This research demonstrated that increased dopamine neurotransmission acts as a sine qua non condition for pleasurable hedonic reactions to music in humans.

A study published in Nature in 1998 found evidence that playing video games releases dopamine in the human striatum. This dopamine is associated with learning, behavior reinforcement, attention, and sensorimotor integration. Researchers used positron emission tomography scans and 11C-labelled raclopride to track dopamine levels in the brain during goal-directed motor tasks and found that dopamine release was positively correlated with task performance and was greatest in the ventral striatum. This was the first study to demonstrate the behavioral conditions under which dopamine is released in humans. It highlights the ability of positron emission tomography to detect neurotransmitter fluxes during changes in behavior. According to research, potentially problematic video game use is related to personality traits such as low self-esteem and low self-efficacy, anxiety, aggression, and clinical symptoms of depression and anxiety disorders. Additionally, the reasons individuals play video games vary and may include coping, socialization, and personal satisfaction. The DSM-5 defines Internet Gaming Disorder as a mental disorder closely related to Gambling Disorder. This has been supported by some researchers but has also caused controversy.

Outside the central nervous system
Dopamine does not cross the blood–brain barrier, so its synthesis and functions in peripheral areas are to a large degree independent of its synthesis and functions in the brain. A substantial amount of dopamine circulates in the bloodstream, but its functions there are not entirely clear. Dopamine is found in blood plasma at levels comparable to those of epinephrine, but in humans, over 95% of the dopamine in the plasma is in the form of dopamine sulfate, a conjugate produced by the enzyme sulfotransferase 1A3/1A4 acting on free dopamine. The bulk of this dopamine sulfate is produced in the mesenteric organs. The production of dopamine sulfate is thought to be a mechanism for detoxifying dopamine that is ingested as food or produced by the digestive process—levels in the plasma typically rise more than fifty-fold after a meal. Dopamine sulfate has no known biological functions and is excreted in urine.

The relatively small quantity of unconjugated dopamine in the bloodstream may be produced by the sympathetic nervous system, the digestive system, or possibly other organs. It may act on dopamine receptors in peripheral tissues, or be metabolized, or be converted to norepinephrine by the enzyme dopamine beta hydroxylase, which is released into the bloodstream by the adrenal medulla. Some dopamine receptors are located in the walls of arteries, where they act as a vasodilator and an inhibitor of norepinephrine release from postganglionic sympathetic nerves terminals (dopamine can inhibit norepinephrine release by acting on presynaptic dopamine receptors, and also on presynaptic α-1 receptors, like norepinephrine itself). These responses might be activated by dopamine released from the carotid body under conditions of low oxygen, but whether arterial dopamine receptors perform other biologically useful functions is not known.

Beyond its role in modulating blood flow, there are several peripheral systems in which dopamine circulates within a limited area and performs an exocrine or paracrine function. The peripheral systems in which dopamine plays an important role include the immune system, the kidneys and the pancreas.

Immune system
In the immune system dopamine acts upon receptors present on immune cells, especially lymphocytes. Dopamine can also affect immune cells in the spleen, bone marrow, and circulatory system. In addition, dopamine can be synthesized and released by immune cells themselves. The main effect of dopamine on lymphocytes is to reduce their activation level. The functional significance of this system is unclear, but it affords a possible route for interactions between the nervous system and immune system, and may be relevant to some autoimmune disorders.

Kidneys
The renal dopaminergic system is located in the cells of the nephron in the kidney, where all subtypes of dopamine receptors are present. Dopamine is also synthesized there, by tubule cells, and discharged into the tubular fluid. Its actions include increasing the blood supply to the kidneys, increasing the glomerular filtration rate, and increasing the excretion of sodium in the urine. Hence, defects in renal dopamine function can lead to reduced sodium excretion and consequently result in the development of high blood pressure. There is strong evidence that faults in the production of dopamine or in the receptors can result in a number of pathologies including oxidative stress, edema, and either genetic or essential hypertension. Oxidative stress can itself cause hypertension. Defects in the system can also be caused by genetic factors or high blood pressure.

Pancreas
In the pancreas the role of dopamine is somewhat complex. The pancreas consists of two parts, an exocrine and an endocrine component. The exocrine part synthesizes and secretes digestive enzymes and other substances, including dopamine, into the small intestine. The function of this secreted dopamine after it enters the small intestine is not clearly established—the possibilities include protecting the intestinal mucosa from damage and reducing gastrointestinal motility (the rate at which content moves through the digestive system).

The pancreatic islets make up the endocrine part of the pancreas, and synthesize and secrete hormones including insulin into the bloodstream. There is evidence that the beta cells in the islets that synthesize insulin contain dopamine receptors, and that dopamine acts to reduce the amount of insulin they release. The source of their dopamine input is not clearly established—it may come from dopamine that circulates in the bloodstream and derives from the sympathetic nervous system, or it may be synthesized locally by other types of pancreatic cells.

Medical uses

Dopamine as a manufactured medication is sold under the trade names Intropin, Dopastat, and Revimine, among others. It is on the World Health Organization's List of Essential Medicines. It is most commonly used as a stimulant drug in the treatment of severe low blood pressure, slow heart rate, and cardiac arrest. It is especially important in treating these in newborn infants. It is given intravenously. Since the half-life of dopamine in plasma is very short—approximately one minute in adults, two minutes in newborn infants and up to five minutes in preterm infants—it is usually given in a continuous intravenous drip rather than a single injection.

Its effects, depending on dosage, include an increase in sodium excretion by the kidneys, an increase in urine output, an increase in heart rate, and an increase in blood pressure. At low doses it acts through the sympathetic nervous system to increase heart muscle contraction force and heart rate, thereby increasing cardiac output and blood pressure. Higher doses also cause vasoconstriction that further increases blood pressure. Older literature also describes very low doses thought to improve kidney function without other consequences, but recent reviews have concluded that doses at such low levels are not effective and may sometimes be harmful. While some effects result from stimulation of dopamine receptors, the prominent cardiovascular effects result from dopamine acting at α1, β1, and β2 adrenergic receptors.

Side effects of dopamine include negative effects on kidney function and irregular heartbeats. The LD50, or lethal dose which is expected to prove fatal in 50% of the population, has been found to be: 59 mg/kg (mouse; administered intravenously); 95 mg/kg (mouse; administered intraperitoneally); 163 mg/kg (rat; administered intraperitoneally); 79 mg/kg (dog; administered intravenously).

Disease, disorders, and pharmacology
The dopamine system plays a central role in several significant medical conditions, including Parkinson's disease, attention deficit hyperactivity disorder, Tourette syndrome, schizophrenia, bipolar disorder, and addiction. Aside from dopamine itself, there are many other important drugs that act on dopamine systems in various parts of the brain or body. Some are used for medical or recreational purposes, but neurochemists have also developed a variety of research drugs, some of which bind with high affinity to specific types of dopamine receptors and either agonize or antagonize their effects, and many that affect other aspects of dopamine physiology, including dopamine transporter inhibitors, VMAT inhibitors, and enzyme inhibitors.

Aging brain
A number of studies have reported an age-related decline in dopamine synthesis and dopamine receptor density (i.e., the number of receptors) in the brain. This decline has been shown to occur in the striatum and extrastriatal regions. Decreases in the D1, D2, and D3 receptors are well documented. The reduction of dopamine with aging is thought to be responsible for many neurological symptoms that increase in frequency with age, such as decreased arm swing and increased rigidity. Changes in dopamine levels may also cause age-related changes in cognitive flexibility.

Multiple sclerosis
Studies reported that dopamine imbalance influences the fatigue in multiple sclerosis. In patients with multiple sclerosis, dopamine inhibits production of IL-17 and IFN-γ by peripheral blood mononuclear cells.

Parkinson's disease
Parkinson's disease is an age-related disorder characterized by movement disorders such as stiffness of the body, slowing of movement, and trembling of limbs when they are not in use. In advanced stages it progresses to dementia and eventually death. The main symptoms are caused by the loss of dopamine-secreting cells in the substantia nigra. These dopamine cells are especially vulnerable to damage, and a variety of insults, including encephalitis (as depicted in the book and movie Awakenings), repeated sports-related concussions, and some forms of chemical poisoning such as MPTP, can lead to substantial cell loss, producing a parkinsonian syndrome that is similar in its main features to Parkinson's disease. Most cases of Parkinson's disease, however, are idiopathic, meaning that the cause of cell death cannot be identified.

The most widely used treatment for parkinsonism is administration of L-DOPA, the metabolic precursor for dopamine. L-DOPA is converted to dopamine in the brain and various parts of the body by the enzyme DOPA decarboxylase. L-DOPA is used rather than dopamine itself because, unlike dopamine, it is capable of crossing the blood–brain barrier. It is often co-administered with an enzyme inhibitor of peripheral decarboxylation such as carbidopa or benserazide, to reduce the amount converted to dopamine in the periphery and thereby increase the amount of L-DOPA that enters the brain. When L-DOPA is administered regularly over a long time period, a variety of unpleasant side effects such as dyskinesia often begin to appear; even so, it is considered the best available long-term treatment option for most cases of Parkinson's disease.

L-DOPA treatment cannot restore the dopamine cells that have been lost, but it causes the remaining cells to produce more dopamine, thereby compensating for the loss to at least some degree. In advanced stages the treatment begins to fail because the cell loss is so severe that the remaining ones cannot produce enough dopamine regardless of L-DOPA levels. Other drugs that enhance dopamine function, such as bromocriptine and pergolide, are also sometimes used to treat Parkinsonism, but in most cases L-DOPA appears to give the best trade-off between positive effects and negative side-effects.

Dopaminergic medications that are used to treat Parkinson's disease are sometimes associated with the development of a dopamine dysregulation syndrome, which involves the overuse of dopaminergic medication and medication-induced compulsive engagement in natural rewards like gambling and sexual activity. The latter behaviors are similar to those observed in individuals with a behavioral addiction.

Drug addiction and psychostimulants

Cocaine, substituted amphetamines (including methamphetamine), Adderall, methylphenidate (marketed as Ritalin or Concerta), and other psychostimulants exert their effects primarily or partly by increasing dopamine levels in the brain by a variety of mechanisms. Cocaine and methylphenidate are dopamine transporter blockers or reuptake inhibitors; they non-competitively inhibit dopamine reuptake, resulting in increased dopamine concentrations in the synaptic cleft. Like cocaine, substituted amphetamines and amphetamine also increase the concentration of dopamine in the synaptic cleft, but by different mechanisms.

The effects of psychostimulants include increases in heart rate, body temperature, and sweating; improvements in alertness, attention, and endurance; increases in pleasure produced by rewarding events; but at higher doses agitation, anxiety, or even loss of contact with reality. Drugs in this group can have a high addiction potential, due to their activating effects on the dopamine-mediated reward system in the brain. However some can also be useful, at lower doses, for treating attention deficit hyperactivity disorder (ADHD) and narcolepsy. An important differentiating factor is the onset and duration of action. Cocaine can take effect in seconds if it is injected or inhaled in free base form; the effects last from 5 to 90 minutes. This rapid and brief action makes its effects easily perceived and consequently gives it high addiction potential. Methylphenidate taken in pill form, in contrast, can take two hours to reach peak levels in the bloodstream, and depending on formulation the effects can last for up to 12 hours. These longer acting formulations have the benefit of reducing the potential for abuse, and improving adherence for treatment by using more convenient dosage regimens.

A variety of addictive drugs produce an increase in reward-related dopamine activity. Stimulants such as nicotine, cocaine and methamphetamine promote increased levels of dopamine which appear to be the primary factor in causing addiction. For other addictive drugs such as the opioid heroin, the increased levels of dopamine in the reward system may play only a minor role in addiction. When people addicted to stimulants go through withdrawal, they do not experience the physical suffering associated with alcohol withdrawal or withdrawal from opiates; instead they experience craving, an intense desire for the drug characterized by irritability, restlessness, and other arousal symptoms, brought about by psychological dependence.

The dopamine system plays a crucial role in several aspects of addiction. At the earliest stage, genetic differences that alter the expression of dopamine receptors in the brain can predict whether a person will find stimulants appealing or aversive. Consumption of stimulants produces increases in brain dopamine levels that last from minutes to hours. Finally, the chronic elevation in dopamine that comes with repetitive high-dose stimulant consumption triggers a wide-ranging set of structural changes in the brain that are responsible for the behavioral abnormalities which characterize an addiction. Treatment of stimulant addiction is very difficult, because even if consumption ceases, the craving that comes with psychological withdrawal does not. Even when the craving seems to be extinct, it may re-emerge when faced with stimuli that are associated with the drug, such as friends, locations and situations. Association networks in the brain are greatly interlinked.

Psychosis and antipsychotic drugs
Psychiatrists in the early 1950s discovered that a class of drugs known as typical antipsychotics (also known as major tranquilizers), were often effective at reducing the psychotic symptoms of schizophrenia. The introduction of the first widely used antipsychotic, chlorpromazine (Thorazine), in the 1950s, led to the release of many patients with schizophrenia from institutions in the years that followed. By the 1970s researchers understood that these typical antipsychotics worked as antagonists on the D2 receptors. This realization led to the so-called dopamine hypothesis of schizophrenia, which postulates that schizophrenia is largely caused by hyperactivity of brain dopamine systems. The dopamine hypothesis drew additional support from the observation that psychotic symptoms were often intensified by dopamine-enhancing stimulants such as methamphetamine, and that these drugs could also produce psychosis in healthy people if taken in large enough doses. In the following decades other atypical antipsychotics that had fewer serious side effects were developed. Many of these newer drugs do not act directly on dopamine receptors, but instead produce alterations in dopamine activity indirectly. These drugs were also used to treat other psychoses. Antipsychotic drugs have a broadly suppressive effect on most types of active behavior, and particularly reduce the delusional and agitated behavior characteristic of overt psychosis.

Later observations, however, have caused the dopamine hypothesis to lose popularity, at least in its simple original form. For one thing, patients with schizophrenia do not typically show measurably increased levels of brain dopamine activity. Even so, many psychiatrists and neuroscientists continue to believe that schizophrenia involves some sort of dopamine system dysfunction. As the "dopamine hypothesis" has evolved over time, however, the sorts of dysfunctions it postulates have tended to become increasingly subtle and complex.

Psychopharmacologist Stephen M. Stahl suggested in a review of 2018 that in many cases of psychosis, including schizophrenia, three interconnected networks based on dopamine, serotonin, and glutamate – each on its own or in various combinations – contributed to an overexcitation of dopamine D2 receptors in the ventral striatum.

Attention deficit hyperactivity disorder
Altered dopamine neurotransmission is implicated in attention deficit hyperactivity disorder (ADHD), a condition associated with impaired cognitive control, in turn leading to problems with regulating attention (attentional control), inhibiting behaviors (inhibitory control), and forgetting things or missing details (working memory), among other problems. There are genetic links between dopamine receptors, the dopamine transporter, and ADHD, in addition to links to other neurotransmitter receptors and transporters. The most important relationship between dopamine and ADHD involves the drugs that are used to treat ADHD. Some of the most effective therapeutic agents for ADHD are psychostimulants such as methylphenidate (Ritalin, Concerta) and amphetamine (Evekeo, Adderall, Dexedrine), drugs that increase both dopamine and norepinephrine levels in the brain. The clinical effects of these psychostimulants in treating ADHD are mediated through the indirect activation of dopamine and norepinephrine receptors, specifically dopamine receptor D1 and adrenoceptor α2, in the prefrontal cortex.

Pain
Dopamine plays a role in pain processing in multiple levels of the central nervous system including the spinal cord, periaqueductal gray, thalamus, basal ganglia, and cingulate cortex. Decreased levels of dopamine have been associated with painful symptoms that frequently occur in Parkinson's disease. Abnormalities in dopaminergic neurotransmission also occur in several painful clinical conditions, including burning mouth syndrome, fibromyalgia, and restless legs syndrome.

Nausea
Nausea and vomiting are largely determined by activity in the area postrema in the medulla of the brainstem, in a region known as the chemoreceptor trigger zone. This area contains a large population of type D2 dopamine receptors. Consequently, drugs that activate D2 receptors have a high potential to cause nausea. This group includes some medications that are administered for Parkinson's disease, as well as other dopamine agonists such as apomorphine. In some cases, D2-receptor antagonists such as metoclopramide are useful as anti-nausea drugs.

Microorganisms
There are no reports of dopamine in archaea, but it has been detected in some types of bacteria and in the protozoan called Tetrahymena. Perhaps more importantly, there are types of bacteria that contain homologs of all the enzymes that animals use to synthesize dopamine. It has been proposed that animals derived their dopamine-synthesizing machinery from bacteria, via horizontal gene transfer that may have occurred relatively late in evolutionary time, perhaps as a result of the symbiotic incorporation of bacteria into eukaryotic cells that gave rise to mitochondria.

Animals
Dopamine is used as a neurotransmitter in most multicellular animals. In sponges there is only a single report of the presence of dopamine, with no indication of its function; however, dopamine has been reported in the nervous systems of many other radially symmetric species, including the cnidarian jellyfish, hydra and some corals. This dates the emergence of dopamine as a neurotransmitter back to the earliest appearance of the nervous system, over 500 million years ago in the Cambrian Period. Dopamine functions as a neurotransmitter in vertebrates, echinoderms, arthropods, molluscs, and several types of worm.

In every type of animal that has been examined, dopamine has been seen to modify motor behavior. In the model organism, nematode Caenorhabditis elegans, it reduces locomotion and increases food-exploratory movements; in flatworms it produces "screw-like" movements; in leeches it inhibits swimming and promotes crawling. Across a wide range of vertebrates, dopamine has an "activating" effect on behavior-switching and response selection, comparable to its effect in mammals.

Dopamine has also consistently been shown to play a role in reward learning, in all animal groups. As in all vertebrates – invertebrates such as roundworms, flatworms, molluscs and common fruit flies can all be trained to repeat an action if it is consistently followed by an increase in dopamine levels. In fruit flies, distinct elements for reward learning suggest a modular structure to the insect reward processing system that broadly parallels that in the mammalian one. For example, dopamine regulates short- and long-term learning in monkeys; in fruit flies, different groups of dopamine neurons mediate reward signals for short- and long-term memories.

It had long been believed that arthropods were an exception to this with dopamine being seen as having an adverse effect. Reward was seen to be mediated instead by octopamine, a neurotransmitter closely related to norepinephrine. More recent studies, however, have shown that dopamine does play a part in reward learning in fruit flies. It has also been found that the rewarding effect of octopamine is due to its activating a set of dopaminergic neurons not previously accessed in the research.

Plants

Many plants, including a variety of food plants, synthesize dopamine to varying degrees. The highest concentrations have been observed in bananas—the fruit pulp of red and yellow bananas contains dopamine at levels of 40 to 50 parts per million by weight. Potatoes, avocados, broccoli, and Brussels sprouts may also contain dopamine at levels of 1 part per million or more; oranges, tomatoes, spinach, beans, and other plants contain measurable concentrations less than 1 part per million. The dopamine in plants is synthesized from the amino acid tyrosine, by biochemical mechanisms similar to those that animals use. It can be metabolized in a variety of ways, producing melanin and a variety of alkaloids as byproducts. The functions of plant catecholamines have not been clearly established, but there is evidence that they play a role in the response to stressors such as bacterial infection, act as growth-promoting factors in some situations, and modify the way that sugars are metabolized. The receptors that mediate these actions have not yet been identified, nor have the intracellular mechanisms that they activate.

Dopamine consumed in food cannot act on the brain, because it cannot cross the blood–brain barrier. However, there are also a variety of plants that contain L-DOPA, the metabolic precursor of dopamine. The highest concentrations are found in the leaves and bean pods of plants of the genus Mucuna, especially in Mucuna pruriens (velvet beans), which have been used as a source for L-DOPA as a drug. Another plant containing substantial amounts of L-DOPA is Vicia faba, the plant that produces fava beans (also known as "broad beans"). The level of L-DOPA in the beans, however, is much lower than in the pod shells and other parts of the plant. The seeds of Cassia and Bauhinia trees also contain substantial amounts of L-DOPA.

In a species of marine green algae Ulvaria obscura, a major component of some algal blooms, dopamine is present in very high concentrations, estimated at 4.4% of dry weight. There is evidence that this dopamine functions as an anti-herbivore defense, reducing consumption by snails and isopods.

As a precursor for melanin
Melanins are a family of dark-pigmented substances found in a wide range of organisms. Chemically they are closely related to dopamine, and there is a type of melanin, known as dopamine-melanin, that can be synthesized by oxidation of dopamine via the enzyme tyrosinase. The melanin that darkens human skin is not of this type: it is synthesized by a pathway that uses L-DOPA as a precursor but not dopamine. However, there is substantial evidence that the neuromelanin that gives a dark color to the brain's substantia nigra is at least in part dopamine-melanin.

Dopamine-derived melanin probably appears in at least some other biological systems as well. Some of the dopamine in plants is likely to be used as a precursor for dopamine-melanin. The complex patterns that appear on butterfly wings, as well as black-and-white stripes on the bodies of insect larvae, are also thought to be caused by spatially structured accumulations of dopamine-melanin.

History and development
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England and first identified in the human brain by Katharine Montagu in 1957. It was named dopamine because it is a monoamine whose precursor in the Barger-Ewens synthesis is 3,4-dihydroxyphenylalanine (levodopa or L-DOPA). Dopamine's function as a neurotransmitter was first recognized in 1958 by Arvid Carlsson and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden. Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine for showing that dopamine is not only a precursor of norepinephrine (noradrenaline) and epinephrine (adrenaline), but is also itself a neurotransmitter.

Polydopamine
Research motivated by adhesive polyphenolic proteins in mussels led to the discovery in 2007 that a wide variety of materials, if placed in a solution of dopamine at slightly basic pH, will become coated with a layer of polymerized dopamine, often referred to as polydopamine. This polymerized dopamine forms by a spontaneous oxidation reaction, and is formally a type of melanin. Furthermore, dopamine self-polymerization can be used to modulate the mechanical properties of peptide-based gels. Synthesis of polydopamine usually involves reaction of dopamine hydrochloride with Tris as a base in water. The structure of polydopamine is unknown.

Polydopamine coatings can form on objects ranging in size from nanoparticles to large surfaces. Polydopamine layers have chemical properties that have the potential to be extremely useful, and numerous studies have examined their possible applications. At the simplest level, they can be used for protection against damage by light, or to form capsules for drug delivery. At a more sophisticated level, their adhesive properties may make them useful as substrates for biosensors or other biologically active macromolecules.

title: Dopamine