Methamphetamine-induced alterations in monoamine transport: implications for neurotoxicity, neuroprotection and treatment.
OBJECTIVE
To review studies delineating the neurotoxic effects of methamphetamine on monoamine transport in dopaminergic neurons of the striatum and nucleus accumbens.


METHODS
The scope of this review includes the English language dopamine transporter and vesicular monoamine transporter-2 primary literature to April 2006 identified by Pubmed, Science Citation Index and SciFinder Scholar literature searches.


RESULTS
Changes in the function of the plasmalemmal dopamine transporter and the vesicular monoamine transporter-2 are key components of methamphetamine-induced persistent dopaminergic deficits. These deficits include persistent reductions in dopamine content, dopamine transporter density and tyrosine hydroxylase activity. The striatum is susceptible to these effects of methamphetamine while the nucleus accumbens is resistant. Differences in dopamine transporter density and activity, extracellular dopamine levels and antioxidant levels in these two brain regions may, in part, account for the resistance of the nucleus accumbens.


CONCLUSIONS
These findings concerning the nature of methamphetamine-induced changes in plasmalemmal and vesicular dopamine transport have very important implications for drug targets and for understanding the etiology of dopaminergic neurodegenerative processes, such as those associated with methamphetamine addiction and Parkinson's disease.
Volz
Trent J
TJ
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Fleckenstein
Annette E
AE
Hanson
Glen R
GR
D019969:Amphetamine-Related Disorders / Q000150:complications* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000139:chemically induced*; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000187:drug effects*
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase