Dopamine

Abstract Dopamine is a neurotransmitter (or chemical messenger) found in diverse organisms ranging from invertebrates to humans. It is also a required intermediate in the formation of the neurotransmitters noradrenaline and adrenaline. Although found in a number of vertebrate tissues, dopamine's most important effects are due to robust expression in a relatively small number of central nervous system neurones that have widespread projections. Dopamine signalling affects a correspondingly wide variety of physiological functions, from gastrointestinal motility and pituitary hormone release, to voluntary movements, motivation and reward, and higher cognitive processes. Although dopamine neurotransmission is normally a highly regulated process, drugs have been developed to modify its signalling. Some commonly used drugs affect dopamine neurotransmission indirectly (by changing its synthesis, storage, release, reuptake or inactivation), whereas other drugs more directly mimic or block the actions of dopamine at its biological targets (i.e. multiple cell surface dopamine‐responsive receptors). An astonishingly broad range of central nervous system disorders (including Parkinson disease, schizophrenia, attention deficit hyperactivity disorder and sleep disorders), and other medical conditions (such as nausea, excessive pituitary hormones, gastrointestinal disorders and cardiovascular shock) are currently treated using such drugs. Key Concepts Dopamine is a neurotransmitter in the brain and elsewhere, as well as an intermediate in the biosynthesis of the neurotransmitters noradrenaline and adrenaline. Dopamine synthesis is regulated by a rate‐limiting enzyme, and its extracellular concentrations controlled by an active recapture mechanism and several metabolic enzymes. The effects of dopamine are mediated by a family of G protein‐coupled receptors linked to distinct intracellular signalling pathways. Though relatively few in number, dopamine‐containing neurons originating in the mammalian midbrain send branching fibres that innervate widespread areas of the forebrain. Brain dopamine influences learning and execution of voluntary movements, motivation, reward, attention and working memory. Disturbances in dopamine neurotransmission have been implicated in a number of CNS disorders but shown most conclusively in Parkinson disease and drug abuse. Drugs that modify CNS dopamine neurotransmission are used to treat a variety of disorders including Parkinson disease, schizophrenia, attention deficit hyperactivity disorder, sleep disorders and nausea. Dopamine receptors outside of the CNS are targets in the medical treatment of excessive pituitary hormone release, certain gastrointestinal disorders and cardiovascular shock. The extensive study of this simple neurotransmitter system has led to fundamental discoveries regarding cellular and molecular mechanisms contributing to normal brain function and human disease.