We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse.
- Authors
Baker, David A; McFarland, Krista; Lake, Russell W; Shen, Hui; Tang, Xing-Chun; Toda, Shigenobu; Kalivas, Peter W
- Abstract
Repeated cocaine treatment and withdrawal produces changes in brain function thought to be involved in relapse to drug use. Withdrawal from repeated cocaine reduced in vivo extracellular glutamate in the nucleus accumbens of rats by decreasing the exchange of extracellular cystine for intracellular glutamate. In vivo restoration of cystine/glutamate exchange by intracranial perfusion of cystine or systemically administered N-acetylcysteine normalized the levels of glutamate in cocaine-treated subjects. To determine if the reduction in nonvesicular glutamate release is a mediator of relapse, we examined cocaine-primed reinstatement of drug seeking after cocaine self-administration was stopped. Reinstatement was prevented by stimulating cystine/glutamate exchange with N-acetylcysteine and restoring extracellular glutamate. Thus, withdrawal from repeated cocaine increases susceptibility to relapse in part by reducing cystine/glutamate exchange, and restoring exchanger activity prevents cocaine-primed drug seeking.
- Publication
Nature neuroscience, 2003, Vol 6, Issue 7, p743
- ISSN
1097-6256
- Publication type
Journal Article
- DOI
10.1038/nn1069