Bupropion increases striatal vesicular monoamine transport.
The vesicular monoamine transporter-2 (VMAT-2) is principally involved in regulating cytoplasmic dopamine (DA) concentrations within terminals by sequestering free DA into synaptic vesicles. This laboratory previously identified a correlation between striatal vesicular DA uptake through VMAT-2 and inhibition of the DA transporter (DAT). For example, administration of methylphenidate (MPD), a DAT inhibitor, increases vesicular DA uptake through VMAT-2 in a purified vesicular preparation; an effect associated with a redistribution of VMAT-2 protein within DA terminals. The purpose of this study was to determine if other DAT inhibitors, including bupropion, similarly affect VMAT-2. Results revealed bupropion rapidly, reversibly, and dose-dependently increased vesicular DA uptake; an effect also associated with VMAT-2 protein redistribution. The bupropion-induced increase in vesicular DA uptake was prevented by pretreatment with eticlopride, a DA D2 receptor antagonist, but not by SCH23390, a DA D1 receptor antagonist. We previously reported that MPD post-treatment prevents persistent DA deficits associated with multiple methamphetamine (METH) administrations. Although bupropion attenuated the METH-induced reduction in VMAT-2 activity acutely, it did not prevent the long-term dopaminergic toxicity or the METH-induced redistribution of VMAT-2 protein. The findings from this study demonstrate similarities and differences in the mechanism by which MPD and bupropion affect striatal dopaminergic nerve terminals.
Rau
Kristi S
KS
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Birdsall
Elisabeth
E
Hanson
Jarom E
JE
Johnson-Davis
Kamisha L
KL
Carroll
F Ivy
FI
Wilkins
Diana G
DG
Gibb
James W
JW
Hanson
Glen R
GR
Fleckenstein
Annette E
AE
D000704:Analysis of Variance; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D016642:Bupropion / Q000494:pharmacology*; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium / Q000493:pharmacokinetics; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D016642:Bupropion; D014316:Tritium; D008694:Methamphetamine; D004298:Dopamine