Journal
NEUROPSYCHOPHARMACOLOGY
Volume 28, Issue 1, Pages 73-76Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/sj.npp.1300011
Keywords
cocaine; glutamate; dopamine; place conditioning; ventral tegmental area; NMDA receptor antagonist; AMPA receptor antagonist
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Funding
- NIDA NIH HHS [DA-06214] Funding Source: Medline
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA006214, R37DA006214] Funding Source: NIH RePORTER
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Cocaine administration induces glutamatergic activation within the mesolimbic-accumbens system. This activation has been linked to the behavioral effects of cocaine and recently to the induction of long-term potentiation in dopamine neurons within the ventral tegmental area (VTA). We sought to determine if glutamate receptor activation is also crucial to the development of a conditioned place preference (CPP) to cocaine's rewarding effects. Two groups of rats were given intra-VTA injections of either vehicle or a combination of NMDA (N-methyl-D-aspartate) and AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonists (AP5 0.24 nmol plus CNQX 0.12 nmol per side) prior to each cocaine place-conditioning trial. Microinjections of the glutamate antagonists completely blocked the development of a cocaine CPP when given within, but not when given outside of, the VTA. These data indicate that glutamatergic activity in the VTA may be crucial for learning to associate environmental stimuli with cocaine exposure.
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