期刊
NEUROPHARMACOLOGY
卷 53, 期 8, 页码 958-966出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2007.09.007
关键词
nicotine; corticotropin-releasing factor; norepinephrine; withdrawal; rats
资金
- NIDA NIH HHS [R03 DA020504-02, 1R03DA020504-01, R03 DA020504, R03 DA020504-01] Funding Source: Medline
- NATIONAL INSTITUTE ON DRUG ABUSE [R03DA020504] Funding Source: NIH RePORTER
Tobacco dependence is a chronic disorder that is characterized by relapse after periods of abstinence. It has been hypothesized that the activation of brain stress systems mediates stress-induced relapse to smoking. The aim of these experiments was to investigate the role of corticotropin-releasing factor (CRF) and norepinephrine in stress-induced reinstatement of extinguished nicotine-seeking behavior. Rats were allowed to self-administer nicotine under a fixed-ratio 5 schedule for 14 days and then nicotine-seeking behavior was extinguished by substituting saline for nicotine. In experiment 1, footshocks reinstated extinguished nicotine-seeking behavior. In experiment 2, there was a trend for the CRF1/2 receptor antagonist D-Phe CRF(12-41) (5, 25 mu g, icv) to decrease stress-induced reinstatement of nicotine-seeking behavior. Footshock-induced reinstatement of nicotine-seeking behavior was observed only in a subset of stress-responsive rats (71%). D-Phe CRF(12-41) significantly attenuated stress-induced reinstatement of nicotine-seeking behavior in this subset of rats. In experiment 3, the alpha 2-adrenergic receptor agonist clonidine (20, 40 mu g/kg, sc) attenuated footshock-induced reinstatement of nicotine-seeking behavior. In experiment 4, the effects Of D-Phe CRF(12-41) and clonidine on responding for chocolate-flavored food pellets was investigated in order to determine if these compounds have sedative effects. D-Phe CRF(12-41) did not affect responding for food pellets. Clonidine slightly, but significantly, decreased responding for food pellets. Clonidine decreased responding for food to a lesser degree than it decreased stress-induced reinstatement of nicotine-seeking behavior. These data provide support for the hypothesis that an increased activity of brain CRF and norepinephrine systems mediates stress-induced relapse to nicotine-seeking behavior. Published by Elsevier Ltd.
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