Bupropion increases striatal vesicular monoamine transport

Neuropharmacology. 2005 Nov;49(6):820-30. doi: 10.1016/j.neuropharm.2005.05.004. Epub 2005 Jul 7.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Biological Transport / drug effects
  • Blotting, Western / methods
  • Bupropion / pharmacology*
  • Corpus Striatum / cytology*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Dopamine / pharmacokinetics
  • Dopamine Uptake Inhibitors / metabolism
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Male
  • Methamphetamine / metabolism
  • Methamphetamine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism
  • Synaptic Vesicles / drug effects*
  • Synaptic Vesicles / metabolism
  • Time Factors
  • Tissue Distribution
  • Tritium / pharmacokinetics
  • Vesicular Monoamine Transport Proteins / metabolism


  • Dopamine Uptake Inhibitors
  • Slc18a2 protein, rat
  • Vesicular Monoamine Transport Proteins
  • Bupropion
  • Tritium
  • Methamphetamine
  • Dopamine