期刊
PSYCHOPHARMACOLOGY
卷 225, 期 2, 页码 473-482出版社
SPRINGER
DOI: 10.1007/s00213-012-2837-3
关键词
Motivation; Extinction; Glutamate; Food responding; Drug abuse; Dependence
资金
- National Institutes of Health [DA11946]
- National Science Foundation [HRD-0331537]
- Tobacco-Related Disease Research Program (TRDRP) of the State of California Individual Post-doctoral Fellowship [19FT-0045]
- Bristol-Myers Squibb Co.
- F. Hoffman-La Roche
- Pfizer
- Astra-Zeneca
- Abbott GmbH and Company
- AstraZeneca
Chronic nicotine administration decreases the functioning of the cystine-glutamate antiporter system x(c)- which is hypothesized to promote nicotine-taking and nicotine-seeking behaviors. N-acetylcysteine (NAC), a cystine pro-drug, increases the activity of the cystine-glutamate antiporter system x(c)-. Thus, NAC could potentially reverse nicotine-induced alterations in glutamatergic transmission and decrease nicotine taking and seeking. To test this hypothesis in the present study, the effects of acute NAC treatment (30, 60, and 90 mg/kg, i.p.) on nicotine (fixed- and progressive-ratio schedules) and food (fixed-ratio schedule) self-administration were assessed in rats. In addition, the effects of acute NAC treatment on cue-induced reinstatement of nicotine- and food-seeking behaviors were investigated. Finally, the effects of repeated daily NAC administration (60 mg/kg, i.p., 14 days) on nicotine and food self-administration were assessed. Acute NAC administration decreased nicotine self-administration but not food responding under a fixed-ratio schedule of reinforcement. In addition, acute NAC administration showed a nonsignificant trend in attenuating nicotine self-administration under a progressive-ratio schedule that was similar to the dose-response function under the fixed-ratio schedule. Furthermore, repeated NAC administration decreased nicotine self-administration from day 6 to 14 compared with vehicle treatment, with no indication of tolerance development. By contrast, repeated NAC administration decreased food responding from day 6 to 8 compared with vehicle treatment and showed rapid development of tolerance. Finally, acute NAC administration attenuated cue-induced reinstatement of nicotine and food seeking. Altogether, these findings suggest that NAC may be useful in promoting smoking cessation in humans.
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