大鼠配对前经历吗啡成瘾及戒断对子代焦虑样行为产生的机制  

Mechanism of adult offspring rats＇ anxiety-like behavior induced by morphine addiction and withdrawal in parents before mating

作　　者：罗雁威[1] 曹文宇[1] 徐杨[1] 钟小林[1] 王雪琴[1] 段娟[1] 李芳[1] 张建一[1] 李昌琪[1] 

机构地区：[1]410013长沙,中南大学基础医学院人体解剖学与神经生物学系

出　　处：《中华行为医学与脑科学杂志》2012年第6期500-504,共5页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目（30971533）

摘　　要：目的探讨亲代大鼠配对前经历吗啡成瘾及戒断对子代焦虑样行为产生的机制。方法选用8周Sprague—Dawley大鼠（雌雄各半）建立吗啡依赖模型，自然戒断21d后配对分组合笼，同时建立生理盐水对照组。子代鼠8周时，雌雄各5只取脑通过Golgi—Cox染色观察子鼠海马CAl区神经元树突形态情况；另外，子代鼠雌雄再各取5只，深度麻醉后取海马组织作全基因组表达谱分析。结果吗啡成瘾组子代海马CA1区神经元基树突分枝总长度和基树突分支个数低于对照组子代∽〈0．05）；吗啡成瘾组子代与对照组子代相比，雄性子代鼠共同表达2倍上调的有663个基因，共同表达2倍下调的有449个基因，雌性子代鼠共同表达2倍上调的有350个基因，共同表达2倍下调的有188个基因；其中与睛绪行为调节相关的基因有：5-HT2。受体上调7倍，Igf-2上调7．1倍，reelin表达下调3．3倍。结论亲代经历吗啡成瘾戒断导致子代海马CAl区神经元树突发育不良，5-HT2c、Igf-2、reelin等基因表达异常，这可能是子代焦虑样行为产生的原因。Objective To explore the possible mechanism of aduh offspring rats＇anxiety-like behavior in- duced by parents experienced morphine addiction and withdrawal. Methods Establishing the model of Sprague- Dawley rats morphine addiction, Male and female rats were mated after morphine withdrawal 21 days. Meaningwhile, saline control group was established in the same method. 5 female and 5 male offspring＇s brains were obtained to observe the neuronal morphology of hippocampal CA1 through Golgi staining when they were 8 weeks old, the same number of female and male＇s hippocampus were derived after deeply anesthetized to perform the whole ge- home expression profiles analysis. Results The total length and the number of basal dendrites branches on hippocampal CA1 neurons in offspring of morphine groups were significantly decreased compared to the offspring of saline group. Comparison with the offspring of saline group,663 up-regulated genes （ratios ≥ 2.0） and 499 down- regulated genes （ ratios ≤0.5 ） were detected in the male offspring of morphine groups, and 350 up-regulated genes （ratios 〉~2.0） and 188 down-regulated genes （ratios ≤0.5 ） were done in the female. Furthermore ,they includ- ed many genes associated with regulation of emotional behavior, such as 5-HT2c receptor up-regulation 7-fold, Igf-2 up-regulation 7. 1-fold and reelin down-regulation 3.3-fold were observed. Conclusion Experienced morphine addiction and withdrawal in parents prior to mating leads to dysplasia of dendritic morphology in hippocampal CAI neurons of adult offspring rats, and 5-HT2c, Igf-2, reelin expressing abnormally, which may be the possible mechanism of anxiety-like behavior in adult offspring rats.

关 键 词：吗啡成瘾 戒断 焦虑样行为 基因芯片 海马 子代 

分 类 号：R749.64[医药卫生—神经病学与精神病学]