Document Detail


Psychostimulants and vesicle trafficking: a novel mechanism and therapeutic implications.
MedLine Citation:
PMID:  15542712     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The monoamine vesicular transporter 2 (VMAT-2) has been associated with dopamine (DA) sequestration and protection against neurodegeneration caused by the intracellular oxidation of this monoamine. The data presented herein suggest that methylphenidate treatment enhances the amount of VMAT-2 protein and possibly its activity in the presynaptic cytosol, where it is able to increase the sequestration of DA and likely protect against its instability. In contrast, methamphetamine (METH) has an opposite effect on cytosolic VMAT-2 resulting in degradation of DA terminals. The fact that posttreatment of methylphenidate after a neurotoxic regimen of METH protects against resulting loss of DA parameters suggests that treatment with methylphenidate, or other DA transporter blockers, may be protective against degenerative disorders of DA pathways, such as Parkinson's disease.
Authors:
Glen R Hanson; Veronica Sandoval; Evan Riddle; Annette E Fleckenstein
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1025     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-11-15     Completed Date:  2005-02-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  146-50     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA. glen.hanson@hsc.utah.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Central Nervous System Stimulants / pharmacology,  therapeutic use
Corpus Striatum / drug effects,  metabolism
Male
Membrane Glycoproteins / metabolism*
Membrane Transport Proteins / metabolism*
Methamphetamine / pharmacology*,  therapeutic use*
Methylphenidate / pharmacology*,  therapeutic use*
Neurodegenerative Diseases / drug therapy,  metabolism
Protein Transport / drug effects,  physiology
Rats
Rats, Sprague-Dawley
Vesicular Biogenic Amine Transport Proteins
Grant Support
ID/Acronym/Agency:
DA 00869/DA/NIDA NIH HHS; DA 11389/DA/NIDA NIH HHS; DA00378/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Central Nervous System Stimulants; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Vesicular Biogenic Amine Transport Proteins; 113-45-1/Methylphenidate; 537-46-2/Methamphetamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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