Individual and combined effects of ethanol and cocaine on the human dopamine transporter in neuronal cell lines.
Concurrent use of cocaine and alcohol results in reinforced behavioral consequences, but the molecular mechanisms associated with the co-use of both drugs are not clear. We report here that a 24-h exposure of the human dopamine transporter (hDAT)-transfected mouse neuroblastoma N1E-115 cell line (6C6) to cocaine (1 microM), or ethanol (1%) or both, increased dopamine re-uptake by approximately 25, 29 and 44%, respectively. The same treatment also increased dopamine re-uptake by the hDAT-transfected mouse neuroblastoma Neuro2A cell line (3B7) by approximately 36, 41 and 77%, respectively. However, no increase of dopamine re-uptake was observed in the hDAT-transfected non-neuronal CHO cell line (10E9). These data support the hypothesis that the DAT may be a common neural substrate for cocaine and ethanol in dopaminergic neurons and it may be involved in the psychological effects of both addictions.
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Department of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
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D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D009419:Nerve Tissue Proteins; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493215:Slc6a3 protein, mouse; D000431:Ethanol; D003042:Cocaine; D004298:Dopamine