Molecular biology, pharmacology and functional role of the plasma membrane dopamine transporter

CNS Neurol Disord Drug Targets. 2006 Feb;5(1):45-56. doi: 10.2174/187152706784111579.

Abstract

The plasma membrane dopamine transporter (DAT) tightly regulates the extracellular concentrations of dopamine (DA) by re-capturing released neurotransmitter back into the presynaptic neuronal terminals and/or neighboring DA projections thereby providing an effective way to regulate synaptic and extrasynaptic DA levels. This transporter is a primary target of many potent psychotropic drugs and neurotoxins, such as cocaine, amphetamines and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this review we summarize recent advances in understanding the structure, regulation, and functional roles of DAT in normal DA physiology and pathological conditions, such as attention deficit hyperactivity disorder (ADHD) and neurodegenerative processes, as well as their contribution to the pharmacology of psychostimulant drugs. Significant new insights on these issues have been gained using mice with genetic deletion of DAT.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / chemistry
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Humans
  • Mental Disorders / drug therapy
  • Mental Disorders / metabolism
  • Mental Disorders / physiopathology
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Psychotropic Drugs / pharmacology
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism*
  • Synaptic Transmission / physiology

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Psychotropic Drugs