Rapid regulation of dopamine transporter function by substrates, blockers and presynaptic receptor ligands

Joshua M. Gulley, Nancy R. Zahniser

Research output: Contribution to journalArticlepeer-review


The extracellular actions of dopamine are terminated primarily through its binding to dopamine transporters and translocation back into dopamine neurons. The transporter thereby serves as an optimal target to regulate dopamine neurotransmission. Although acute pharmacological blockade of dopamine transporters is known to reversibly inhibit transporter function by preventing the binding of its endogenous substrate dopamine, it recently has become clear that dopamine transporter substrates, such as amphetamines, and blockers, such as cocaine, also have the ability to rapidly and persistently regulate transporter function after their direct pharmacological effect has subsided. Presynaptic receptor ligands can also regulate dopamine transporter function. This has been investigated most extensively for dopamine D2 receptors, but there is also evidence for regulation by γ-aminobutyric acid (GABA) GABAB receptors, metabotropic glutamate, nicotinic acetylcholine, serotonin, σ2- and κ-opioid receptors. The focus of this review is the rapid, typically reversible, regulation of dopamine transporter velocity by substrates, blockers and presynaptic receptor ligands. The research discussed here suggests that a common mechanism through which these different classes of compounds regulate transporter activity is by altering the cell surface expression of dopamine transporters.

Original languageEnglish (US)
Pages (from-to)139-152
Number of pages14
JournalEuropean Journal of Pharmacology
Issue number1-3
StatePublished - Oct 31 2003
Externally publishedYes


  • DAT (dopamine transporter)
  • Functional regulation
  • Presynaptic receptor
  • Substrate-mediated regulation
  • Trafficking

ASJC Scopus subject areas

  • Pharmacology


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