Dopamine

Abstract

Dopamine is a neurotransmitter (or chemical messenger) found in diverse organisms ranging from simple 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, 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.

Keywords: neurotransmitter; catecholamine; tyrosine hydroxylase; dopamine transporter; Parkinson disease; reward; addiction; cocaine; amphetamine; schizophrenia; attention deficit hyperactivity disorder

Figure 1.

Biosynthetic pathway of dopamine. Tyrosine hydroxylase is the rate‐limiting step.

Figure 2.

Schematic model of a dopamine synapse. The synthesis, storage, release, reuptake and inactivation of dopamine are depicted. Dopamine interactions with multiple dopamine receptors are also illustrated. (Adapted from Giros B and Caron MG (1993) Trends in Pharmacological Sciences 14: 43–49.)

Figure 3.

Major dopamine‐containing cell groups in the brain and their projections.

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References

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Karam CS, Ballon JS, Bivens NM et al. (2010) Signaling pathways in schizophrenia: Emerging targets and therapeutic strategies. Trends in Pharmacological Sciences 31(8): 381–390.

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Schapira AHV (2009) Neurobiology and treatment of Parkinson's disease. Trends in Pharmacological Sciences 30(1): 41–47.

Wise RA (2009) Role of nigrostriatal‐not just mesocorticolimbic‐dopamine in reward and addiction. Trends in Neurosciences 32(10): 517–524.

Further Reading

Iversen LL (2008) Speed, Ecstasy, Ritalin: The Science of Amphetamines. Oxford: Oxford University Press.

Iversen LL, Iversen SD, Bloom FE and Roth RH (2009) Introduction to Neuropsychopharmacology. Oxford: Oxford University Press.

Kandel ER, Schwartz JH and Jessell TM (eds) (2002) Principles of Neural Science, 4th edn. New York: McGraw‐Hill.

Nestler EJ, Hyman SE and Malenka RC (2009) Molecular Neuropharmacology. A Foundation for Clinical Neuroscience, 2nd edn. New York: McGraw‐Hill.

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How to Cite close
Bannon, Michael J, Bannon, Erin E, and Bannon, Kellen T(Jul 2012) Dopamine. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000279.pub3]