Document Detail


Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1.
MedLine Citation:
PMID:  22079347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that is functionally activated by amphetamine-based psychostimulants, including amphetamine, methamphetamine and MDMA. Previous studies have shown that in transgenic mice lacking the TAAR1 gene (TAAR1 knockout; KO) a single injection of amphetamine can produce enhanced behavioral responses compared to responses evoked in wild-type (WT) mice. Further, the psychostimulant effects of cocaine can be diminished by selective activation of TAAR1. These findings suggest that TAAR1 might be implicated in the rewarding properties of psychostimulants. To investigate the role of TAAR1 in the rewarding effects of drugs of abuse, the psychomotor stimulating effects of amphetamine and methamphetamine and the conditioned rewarding effects of methamphetamine and morphine were compared between WT and TAAR1 KO mice. In locomotor activity studies, both single and repeated exposure to d-amphetamine or methamphetamine generated significantly higher levels of total distance traveled in TAAR1 KO mice compared to WT mice. In conditioned place preference (CPP) studies, TAAR1 KO mice acquired methamphetamine-induced CPP earlier than WT mice and retained CPP longer during extinction training. In morphine-induced CPP, both WT and KO genotypes displayed similar levels of CPP. Results from locomotor activity studies suggest that TAAR1 may have a modulatory role in the behavioral sensitization to amphetamine-based psychostimulants. That methamphetamine-but not morphine-induced CPP was augmented in TAAR1 KO mice suggests a selective role of TAAR1 in the conditioned reinforcing effects of methamphetamine. Collectively, these findings provide support for a regulatory role of TAAR1 in methamphetamine signaling.
Authors:
Cindy Achat-Mendes; Laurie J Lynch; Katherine A Sullivan; Eric J Vallender; Gregory M Miller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-11-04
Journal Detail:
Title:  Pharmacology, biochemistry, and behavior     Volume:  101     ISSN:  1873-5177     ISO Abbreviation:  Pharmacol. Biochem. Behav.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-02-24     Completed Date:  2012-09-24     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  0367050     Medline TA:  Pharmacol Biochem Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  201-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Conditioning (Psychology) / drug effects
Dose-Response Relationship, Drug
Male
Methamphetamine / pharmacology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Motor Activity / drug effects*
Receptors, G-Protein-Coupled / deficiency*,  genetics
Grant Support
ID/Acronym/Agency:
DA025697/DA/NIDA NIH HHS; K02 DA025697/DA/NIDA NIH HHS; K02 DA025697-01A1/DA/NIDA NIH HHS; RR00168/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, G-Protein-Coupled; 0/Trace amine-associated receptor 1; 44RAL3456C/Methamphetamine
Comments/Corrections

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