Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine transporter 2 knock-out mice.
Journal Article (Journal Article)
Methamphetamine (METH) is a powerful psychostimulant that is increasingly abused worldwide. Although it is commonly accepted that the dopaminergic system and oxidation of dopamine (DA) play pivotal roles in the neurotoxicity produced by this phenylethylamine, the primary source of DA responsible for this effect has remained elusive. In this study, we used mice heterozygous for vesicular monoamine transporter 2 (VMAT2 +/- mice) to determine whether impaired vesicular function alters the effects of METH. METH-induced dopaminergic neurotoxicity was increased in striatum of VMAT2 +/- mice compared with wild-type mice as revealed by a more consistent DA and metabolite depletion and a greater decrease in dopamine transporter expression. Interestingly, increased METH neurotoxicity in VMAT2 +/- mice was accompanied by less pronounced increase in extracellular DA and indices of free radical formation compared with wild-type mice. These results indicate that disruption of vesicular monoamine transport potentiates METH-induced neurotoxicity in vivo and point, albeit indirectly, to a greater contribution of intraneuronal DA redistribution rather than extraneuronal overflow on mediating this effect.
Full Text
Duke Authors
Cited Authors
- Fumagalli, F; Gainetdinov, RR; Wang, YM; Valenzano, KJ; Miller, GW; Caron, MG
Published Date
- April 1, 1999
Published In
Volume / Issue
- 19 / 7
Start / End Page
- 2424 - 2431
PubMed ID
- 10087057
Pubmed Central ID
- 10087057
International Standard Serial Number (ISSN)
- 0270-6474
Language
- eng
Conference Location
- United States