利莫那班对药物激发诱导大鼠尼古丁条件性位置偏爱恢复的影响。

Effects of rimonabant on the reinstatement of nicotine-conditioned place preference by drug priming in rats.

作者信息

Biala Grazyna, Budzynska Barbara, Staniak Natasza

机构信息

Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4 Staszica Street, 20-081 Lublin, Poland.

出版信息

Behav Brain Res. 2009 Sep 14;202(2):260-5. doi: 10.1016/j.bbr.2009.03.042. Epub 2009 Apr 8.

Abstract

Drug addiction is a chronic disorder characterized by a relatively high rate of relapse even after long period of abstinence. In the present study, we used the conditioned place preference (CPP) paradigm to investigate the establishment, extinction, reinstatement and cross-reinstatement of nicotine-induced place conditioning in rats. Nicotine produced a place preference to the initially less-preferred compartment paired with its injections during conditioning (0.5mg/kg, i.p., three drug sessions). Once established, nicotine CPP was extinguished by repeated testing. Following this extinction phase, the reinstatement of CPP was investigated. Nicotine-experienced rats were challenged with nicotine (0.5mg/kg, i.p.) or morphine (10mg/kg, i.p.). These priming injections of both drugs induced a marked preference for the compartment previously paired with nicotine. Furthermore, the objective of the present study was to evaluate the efficacy of CB1 cannabinoid receptor antagonist rimonabant (0.5, 1 and 2mg/kg, i.p.) in blocking the reinstatement of nicotine-induced CPP provoked by nicotine and morphine. It was shown that rimonabant attenuated the reinstatement of nicotine-conditioned response induced by both drugs. The outcome of our studies may suggest that CB1 receptor antagonists may become a promising target for effective pharmacotherapy of tobacco addiction and polydrug abuse.

摘要

药物成瘾是一种慢性疾病,其特征是即使经过长时间戒断,复发率仍相对较高。在本研究中,我们使用条件性位置偏爱(CPP)范式来研究大鼠中尼古丁诱导的位置条件反射的建立、消退、恢复和交叉恢复。在条件反射训练期间(0.5mg/kg,腹腔注射,共三次给药),尼古丁与注射配对,使大鼠对最初不太偏爱的隔室产生位置偏爱。一旦建立,尼古丁CPP通过重复测试而消退。在这个消退阶段之后,研究了CPP的恢复情况。让有尼古丁经历的大鼠接受尼古丁(0.5mg/kg,腹腔注射)或吗啡(10mg/kg,腹腔注射)的激发。这两种药物的初次注射均诱导大鼠对先前与尼古丁配对的隔室产生明显偏爱。此外,本研究的目的是评估CB1大麻素受体拮抗剂利莫那班(0.5、1和2mg/kg,腹腔注射)在阻断由尼古丁和吗啡引发的尼古丁诱导的CPP恢复方面的效果。结果表明,利莫那班减弱了这两种药物诱导的尼古丁条件反应的恢复。我们的研究结果可能表明,CB1受体拮抗剂可能成为烟草成瘾和多药滥用有效药物治疗的一个有前景的靶点。

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