期刊
BIOLOGICAL PSYCHIATRY
卷 67, 期 1, 页码 81-84出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2009.07.018
关键词
Cocaine; accumbens; cystine-glutamate exchange; glutamate uptake; GLT-1; self-administration
资金
- NIDA [DA 026010, DA 015369, DA 12,513]
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA003906, P50DA015369, R37DA003906, R01DA012513, R21DA026010] Funding Source: NIH RePORTER
Background: The cystine-glutamate exchanger is downregulated after chronic cocaine, resulting in reduced extracellular levels of nucleus accumbens glutamate. The importance of cocaine-induced loss of glutamate homeostasis is revealed by N-acetylcysteine restoring cystine-glutamate exchange and attenuating reinstatement to cocaine seeking. Another regulator of extracellular glutamate is the glial glutamate transporter GLT-1. We hypothesized that cocaine self-ad ministration reduces GLT-1 and that GLT-1 upregulation inhibits cocaine seeking. Methods: We measured [(3)H] glutamate uptake and protein expression of GLT-1 and xCT, the catalytic subunit of the cystine-glutamate exchanger, following cocaine self-administration and 3 weeks of extinction training. We also examined the affect of ceftriaxone (previously shown to increase GLT-1) and N-acetylcysteine treatment on the expression of GLT-1 and xCT. Ceftriaxone was also tested for the capacity to inhibit cue- and cocaine-induced relapse. Results: Cocaine self-administration reduced glutamate uptake and the expression of both GLT-1 and xCT. Ceftriaxone restored GLT-1 and xCT levels and prevented cue- and cocaine-induced reinstatement of drug seeking. N-acetylcysteine also restored GLT-1 and xCT levels. Conclusions: These results indicate that glutamate transport and cystine-glutamate exchange may be coregulated and provide further evidence that targeting glutamate homeostasis is a potential method for treating cocaine relapse.
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