Dopamine uptake blockers nullify methamphetamine-induced decrease in dopamine uptake and plasma membrane potential in rat striatal synaptosomes.
Rat striatal synaptosomes showed a reduced capacity to generate a membrane potential after being exposed to methamphetamine (METH) for 1 h. As a consequence, the dopamine (DA) synaptosomes were impeded in their electrogenic-dependent reuptake of dopamine. The capacity for METH-exposed nerve terminals to generate a membrane potential may contribute to the ability of METH to destroy dopaminergic neurons. DA uptake inhibitors (DAUIs) were found to counteract the METH-induced decrease in synaptosomal [3H]DA Vmax by stablizing METH-induced reductions in PMP. Because DAUIs showed the same effects as a Na+-channel blocker, DAUIs may prevent METH-induced destruction of dopaminergic neurons by raising plasma membrane potential.
Westphalen
R I
RI
Department of Anatomy, Chinese University of Hong Kong, Shatin, NT. rwestphalen@hotmail.com
Stadlin
A
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology*; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D004338:Drug Combinations; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D008694:Methamphetamine / Q000494:pharmacology*; D010949:Plasma / Q000166:cytology; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects* / Q000502:physiology; D014316:Tritium / Q000493:pharmacokinetics; D014748:Vinca Alkaloids / Q000494:pharmacology
D000975:Antioxidants; D018765:Dopamine Uptake Inhibitors; D004338:Drug Combinations; D014748:Vinca Alkaloids; D014316:Tritium; D008694:Methamphetamine; C013983:vinpocetine; D004298:Dopamine