可卡因戒断后的奖赏改变与下丘脑外侧区食欲素表达

目的：观察下丘脑外侧区食欲素在慢性可卡因戒断后奖赏改变中的作用。方法：大鼠每天进行腹腔注射可卡因,连续10 d（可卡因的剂量从最初的10 mg/kg逐渐增加到第10天的30 mg/kg）,两周可卡因戒断后进行可卡因条件性位置偏爱（CPP）的训练和测试,CPP测试后取大鼠下丘脑脑片行抗Fos和抗食欲素免疫组化双标。结果：与生理盐水组相比,可卡因戒断两周后的大鼠CPP得分明显增加[可卡因戒断组vs生理盐水组：（250±24）svs（132±44）s,P〈0.01];可卡因戒断大鼠下丘脑外侧区Fos阳性神经元的数量比生理盐水组大鼠明显增多[可卡因戒断组vs生理盐水组：（41±4）vs（16±4）,P〈0.05];下丘脑外侧区食欲素阳性神经元中Fos阳性的比例可卡因戒断大鼠也明显提高[可卡因戒断组vs生理盐水组：（39.4±2.4）%vs（22.5±3.2）%,P〈0.01]。大鼠CPP得分和食欲素阳性神经元中Fos阳性的比例呈正相关（R=0.66,P〈0.05）。结论：下丘脑外侧区食欲素可能参与了慢性可卡因戒断后奖赏的改变。

Reward alteration after cocaine abstinent and orexin expression in lateral hypothalamus

AIM：To investigate the role of lateral hypothalamus orexin neurons in the rewarding properties of cocaine during chronic cocaine abstinence. METHODS：Rats were initially treated chronically with daily injections of cocaine（10 days of escalating doses of cocaine,10-30 mg/kg,i.p.）.Following 2 weeks of forced abstinence from cocaine,rats were subjected to a conditioned place preference（CPP）procedure for cocaine.After CPP test,rats were received Fos/Orexin double immunohistochemistry in the lateral hypothalamus.RESULTS：Compared with saline-pretreated group,cocaine preference in abstinent rats was significantly elevated [abstinent rats vs saline rats：（250±24）s vs（132±44）s,cocaine-paired side minus saline-paired side,P0.01];the number of Fos-positive neurons（±SEM） in the lateral hypothalamus in cocaine-treated rats was significantly elevated [cocaine rats vs saline rats：（41±4） vs（16±4）,P0.05];animals that were pretreated with cocaine had a significantly greater percentage of orexin neurons that were Fos-positive [cocaine rats vs saline rats：（39.4±2.4）% vs（22.5±3.2）%,P0.01].A significant correlation was found between the preference scores and the percentage of orexin neurons that were Fos activated（R=0.66,P0.05）.CONCLUSION：Lateral hypothalamus orexin neurons maybe play an important role in the rewarding properties of cocaine during chronic cocaine abstinence.