可卡因戒断后的奖赏改变与下丘脑外侧区食欲素表达

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (9): 986-990.

可卡因戒断后的奖赏改变与下丘脑外侧区食欲素表达

刘胜^1,2, 周文华¹, Gary Aston-Jones²

¹宁波戒毒研究中心,宁波 315010,浙江;
²Medical University of South Carolina, Charleston, SC 29425, USA

收稿日期:2010-07-13 修回日期:2010-09-10 出版日期:2010-09-26 发布日期:2020-09-17
作者简介:刘胜,男,博士,副主任医师,主要从事药物成瘾的基础和临床研究。Tel: 0574-87145142, E-mail: lskingcn@yahoo.com.cn
基金资助:
浙江省中医药科研课题 (2008CA102)和宁波市自然科学基金(2010A610042)联合资助

Reward alteration after cocaine abstinent and orexin expression in lateral hypothalamus

LIU Sheng¹, ZHOU Wen-hua¹, GARY Aston-jonesi²

¹Ningbo Addiction Research and Treatment Center, Ningbo 315010,Zhejiang, China;
²Medical University of South Carolina, Charleston, SC 29425, USA

Received:2010-07-13 Revised:2010-09-10 Online:2010-09-26 Published:2020-09-17

摘要/Abstract

摘要： 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)s vs(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。

关键词: 奖赏, 食欲素, 成瘾, 下丘脑外侧区

Abstract: 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, P<0.01];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), P<0.05]; 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)%, P<0.01]. A significant correlation was found between the preference scores and the percentage of orexin neurons that were Fos activated (R=0.66,P<0.05).CONCLUSION: Lateral hypothalamus orexin neurons maybe play an important role in the rewarding properties of cocaine during chronic cocaine abstinence.

Key words: Reward, Orexin, Addiction, Lateral hypothalamus

中图分类号:

R965.2

刘胜, 周文华, Gary Aston-Jones. 可卡因戒断后的奖赏改变与下丘脑外侧区食欲素表达[J]. 中国临床药理学与治疗学, 2010, 15(9): 986-990.

LIU Sheng, ZHOU Wen-hua, GARY Aston-jonesi. Reward alteration after cocaine abstinent and orexin expression in lateral hypothalamus[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(9): 986-990.

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