中国药理学与毒理学杂志Issue(5)：794-800,7.DOI:10.3867/j.issn.1000-3002.2015.05.055
边缘下皮质脑区微注射克仑特罗对线索诱导海洛因复吸的抑制作用
Infusion of clenbuterol into infralimbic cortex attenuates cue-induced reinstatement of heroin-seeking behavior
摘要
Abstract
OBJECTIVE To investigate the effect of injection of β2-adrenergic receptor agonist clenbuterol into the infralimbic cortex(IL) on drug-seeking behavior triggered by conditioned cues. METHODS Adult male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 d,followed by 2-h extinction training. Cue-induced heroin seeking was measured for 2 h. Clenbuterol was microinjected bilaterally into the IL(8 ng/side)of rats 15 min prior to reinstatement test. Meanwhile,locomotor activity was detected 15 min after clenbuterol or artifial cerebrospinal fluid(mod⁃el group) was microinjected bilaterally into IL. Western blotting was used to detect the expression of phosphorylated cyclic AMP response element-binding protein(p-CREB)in the prelimbic cortex(PL), IL,nucleus accumbens core (NACc) and shell (NACsh) of rats immediately after reinstatement test. RESULTS After heroin administration training for 14 consecutive days,these animals exhibited reliable heroin self-administration,indicated by the increase in active nose poke responses and infusions. The rats that had received infusion of clenbuterol into the IL had significantly lower active pokes (8 ± 3)than those in model group(45±10)in cue-induced reinstatement(P<0.01),but there was no significant differ⁃ence between clenbuterol group and vehicle group in the locomotor activity. The expression of p-CREB in either IL or NACsh was significantly decreased in clenbuterol group compared with model group(P<0.01,P<0.05),but significantly increased in NACc(P<0.01). CONCLUSION Microinjection of clenb⁃uterol into the IL can attenuate the cue-induced reinstatement of heroin-seeking behavior in rats. The underlying mechanism might be related to the regulation of p-CREB expression in the NACc and NACsh.关键词
克仑特罗/边缘下皮质/海洛因/复吸/cAMP反应元件结合蛋白Key words
clenbuterol/infralimbic cortex/heroin/relapse/cyclic AMP response element-binding protein分类
医药卫生引用本文复制引用
王益琦,陈为升,徐文锦,庄丁丁,唐甩恩,朱华强,赖苗军,周文华,刘惠芬..边缘下皮质脑区微注射克仑特罗对线索诱导海洛因复吸的抑制作用[J].中国药理学与毒理学杂志,2015,(5):794-800,7.基金项目
国家自然科学基金重点项目（U1132602）；浙江省自然科学基金面上项目（LY14H310002）；宁波市科技计划项目（2013C50033)@@@@The project supported by National Natural Science Foundation of China（U1132602）；Natural Science Foundation of Zhejiang Provine（LY14H310002）；and Science and Technology Planning Project of Ningbo City （）
