可卡因戒断对小鼠焦虑样行为以及海马神经再生的影响

中国临床解剖学杂志 ›› 2013, Vol. 31 ›› Issue (5): 551-554.

可卡因戒断对小鼠焦虑样行为以及海马神经再生的影响

刘明菲¹，　李娟¹，　顾晶晶¹，　崔梦卿²，　李良平³，　张璐¹

1.南方医科大学病理生理学教研室，广州 510515； 2.南方医科大学南方医院门诊部，广州 510515；
3.广州红十字会医院神经外科，广州 510220

收稿日期:2013-04-20 出版日期:2013-09-25 发布日期:2013-10-16
通讯作者: 张璐，教授，博士生导师，Tel：020-61648726，E-mail: zlulu70@126.com E-mail:285845796@qq.com
作者简介:刘明菲（1986-），男，湖南株洲人，硕士，主要从事可卡因成瘾机制研究，Tel：（020）62789373
基金资助:
国家自然科学基金(81071120, 81371509)；教育部科学技术研究重点项目(21132)；粤港关键领域重点突破项目(2011A011304001)；广东省产学研合作重大科技专项(2011A090100025)；广州市科技计划项目(7411832133935)；广东省自然科学基金（10151022001000003）。

The effect of cocaine withdrawal on anxiety-like behavior and hippocampal neurogenesis of mice

LIU Ming-fei1, LI Juan1, GU Jing-jing1, CUI Meng-qing2, LI Liang-ping3, ZHANH Lu1

1. Department of Pathophysiology, Southern Medical University, Guangzhou 510515; 2.Outpatient Department, Nanfang Hospital, Southern Medical University, Guangzhou 510515; 3. Neurosurgery Department of Guangzhou Red Cross Hospital, Guangzhou 510220, China

Received:2013-04-20 Online:2013-09-25 Published:2013-10-16

摘要/Abstract

摘要：

目的　观察重复给予可卡因并戒断后对小鼠焦虑样行为以及小鼠海马区齿状回区（dentate 　gyrus，DG）神经再生（neurogenesis）的影响。方法　将19只昆明小鼠随机分为两组，生理盐水组9只，可卡因组10只，腹腔注射生理盐水或可卡因(20 mg·kg-1·d-1)，连续注射14 d，戒断48 h，通过旷场实验（OFT）、高架十字迷宫（EPM）观察小鼠焦虑样行为学变化。免疫荧光实验时，生理盐水组和可卡因组分别5只，给药方法同行为学实验，最后一次注射生理盐水或可卡因同时，腹腔注射BrdU（20 mg/kg per 12 hr）,连续注射48 h。最后一次注射BrdU 24 h后，通过BrdU/Dcx双标的免疫荧光技术观察小鼠海马神经再生情况。结果　可卡因组旷场实验中央停留时间(center-time）明显少于生理盐水组（P<0.01）。可卡因组高架十字迷宫开臂进入次数（open arm-entries）和开臂停留时间（open arm -time）明显少于生理盐水组（P<0.01）。免疫荧光实验显示可卡因组小鼠海马DG区BrdU+/Dcx+细胞明显少于生理盐水组（P<0.01）。结论　可卡因反复给药并戒断后，能诱导焦虑样行为的产生以及降低海马DG区神经再生，而海马区神经再生降低可能参与了焦虑样行为的发生。

关键词: 可卡因戒断, 焦虑, 神经再生, 旷场实验, 高架十字迷宫

Abstract:

Objective　To observe the effect of cocaine withdrawal after repeated cocaine administration on anxiety-like behavior and hippocampal neurogenesis in the dentate gyrus.　Method　The Kuming mice were divided into two groups, with 9 in Group saline and 10 in Group cocaine. All mice received daily intraperitoneal injections of saline or cocaine (20 mg/kg) for 14 consecutive days, then all mice were subject to abstinence for 48 hours after the final injection of cocaine or saline. The Open Field Test (OFT) and the Elevated Plus Maze (EPM) were used to observe the level of anxiety-like behavior. For immuno?覲uorescence, mice were also divided into two groups, 5 in each group. After the final injection of cocaine or saline, mice received intraperitoneal injections of BrdU（20 mg/kg, per 12 hours）for 48 hours. 24 hours after the last injection of BrdU, mice were dissected and BrdU+/Dcx+ double labeled immuno?uorescence was carried out to observe the hippocampal neurogenesis in the dentate gyrus.　Result　The center-time in the OFT was significantly reduced in Group cocaine compared with Group saline(P<0.01). Mice received withdrawal from cocaine showed less open arm-entries and open arm-time in the EPM compared with that received withdrawal from saline(P<0.01). Immuno?覲uorescence revealed that the number of BrdU+/Dcx+ cells significantly decreased in Group cocaine compared with Group saline (P<0.01). Conclusion Cocaine withdrawal after repeated cocaine administration can induce anxiety-like behavior and inhibit neurogenesis, and the inhibited neurogenesis may play important role in cocaine withdrawal-induced anxiety-like behavior.

Key words: Cocaine withdrawal, Anxiety; , Neurogenesis, The Open Field Test, The Elevated Plus Maze

中图分类号:

R338.26

刘明菲, 李娟, 顾晶晶, 崔梦卿, 李良平, 张璐. 可卡因戒断对小鼠焦虑样行为以及海马神经再生的影响[J]. 中国临床解剖学杂志, 2013, 31(5): 551-554.

LIU Meng-Fei, LI Juan, GU Jing-Jing, CUI Meng-Qing, LI Liang-Beng, ZHANG Lu. The effect of cocaine withdrawal on anxiety-like behavior and hippocampal neurogenesis of mice[J]. Chinese Journal Of Clinical Anatomy, 2013, 31(5): 551-554.

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