Dopamine  

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A neurotransmitter associated with movement, attention, learning, and the brain's pleasure and reward system.


"L Dopa fixed me, all right."

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Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is an organic chemical of the catecholamine and phenethylamine families that plays several important roles in the brain and body. 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. 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 seen as the main chemical of pleasure, but the current opinion in pharmacology is that dopamine instead affects incentive salience, meaning that it signals the value of an outcome which motivates the organism to achieve an outcome.

Outside the central nervous system, dopamine functions primarily as a local chemical messenger. In blood vessels, it inhibits norepinephrine release and acts as a vasodilator (at normal concentrations); 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: although it cannot reach the brain from the bloodstream, its peripheral effects make it useful in the treatment of heart failure or shock, especially in newborn babies.

History

Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England. It was named dopamine because it is a monoamine whose precursor in the Barger-Ewens synthesis is 3,4-dihydroxyphenylalanine (levodopamine 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 also a neurotransmitter.

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