Regulation of dopamine transporter function and plasma membrane expression by dopamine, amphetamine, and cocaine.
Pharmacological alterations in dopamine transporter (DAT) function not only modulate dopamine reuptake, but they can induce rapid changes in the plasmalemmal expression of the transporter. By modifying transporter membrane expression, drugs may alter the maximum rate of neurotransmitter clearance, shifting cellular transport capacity and disrupting normal receptor stimulation. DAT-interacting drugs include the illicit and highly abused psychostimulants amphetamine and cocaine. Regulation of transporter activity and plasma membrane expression by these drugs has been implicated in the long-term processes of reward and addiction. This review summarizes the regulation of DAT by transporter substrates and blockers with particular emphasis on the modulation of DAT cell surface expression by acute exposure to amphetamine and cocaine.
Kahlig
Kristopher M
KM
Center for Molecular Neuroscience, Department of Molecular Physiology and Biophysics, Vanderbilt University, 465 21st Ave South, Nashville, TN 37232-8548, USA.
Galli
Aurelio
A
D000661:Amphetamine / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine