Effects of the CRF receptor antagonist D-Phe CRF(12-41) and the α2-adrenergic recpetor agonist clonidine on stress-induced reinstatement of nicotine-seeking behavior in rats
Effects of the CRF receptor antagonist D-Phe CRF(12-41) and the α2-adrenergic recpetor agonist clonidine on stress-induced reinstatement of nicotine-seeking behavior in rats
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DOI：
10.1016/j.neuropharm.2007.09.007
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发表时间：
2007-12-01
影响因子：
4.7
通讯作者：
Bruijnzeel, Adrie W.
中科院分区：
文献类型：
--
作者：
Zislis, George;Desai, Tina V.;Bruijnzeel, Adrie W.
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.
