Urocortin对吗啡成瘾大鼠伏隔核中DA能神经电活动影响及机制研究  

Effects of urocortin on nucleus accumbens DA ergic in morphine addiction rats and its mechanism

作　　者：裴苗 刘新宇 杨帆 刘春娜 PEI Miao;LIU Xin-yu;YANG Fan;LIU Chun-na(Dept of Pharmacology, Jinzhou Medical University, Jinzhou Liaoning 121001, China;Dept of Pharmacy, the Central Hospital of Fushun, Fushun Liaoning 116000, China)

机构地区：[1]锦州医科大学药理学教研室,辽宁锦州121001 [2]抚顺中心医院药剂科,辽宁抚顺116000

出　　处：《中国药理学通报》2020年第10期1440-1444,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81201037);辽宁省重点研发计划指导计划项目(No 2018225030);辽宁省自然基金指导计划(No 2019-ZD-0822,2019-ZD-0821)。

摘　　要：目的研究神经肽(urocortin,UCN)对吗啡成瘾大鼠行为学的作用,探讨其对伏隔核(nucleus accumbens,NAc)神经元异常放电的影响和相关机制,为药物成瘾治疗提供理论基础。方法制备吗啡成瘾大鼠模型,随机分为空白对照组(NG)、吗啡成瘾模型组(MCG)和UCN低、高剂量组(UCN-L,UCN-H)。Koob躯体戒断症状评分法测定UCN对戒断症状的改善作用;Morris水迷宫观察UCN对学习记忆的影响;多管微电泳观察UCN对NAc神经元放电变化规律的作用和对多巴胺(dopamine,DA)能神经元放电模式影响;ELISA法测定脑组织络氨酸羟化酶(tyrosine hydroxylase,TH)的含量。结果 UCN能改善戒断症状;UCN组大鼠在原平台象限游泳时间占总游泳时间的百分比明显增加;UCN组与MCG组比较,NAc神经元平均放电频率下降,TH水平降低(P <0.05)。结论 UCN通过降低脑内TH水平,抑制吗啡成瘾大鼠NAc的DA神经元异常兴奋,改善吗啡成瘾的行为学指标,并增强学习记忆能力。Aim To study the effects of neuropeptide urocortin(UCN)on behavior of morphine-addicted rats,and to further explore the effects of UCN on abnormal discharge of neurons of nucleus accumbens(NAc)and the related mechanisms so as to provide a theoretical basis for clinical withdrawal treatment of drug addiction.Methods Morphine administration of sequential incremental method was used to make morphine addiction rat model.Forty rats were divided into four groups,namely,normal group,morphine addiction control group and UCN groups.Koob’s method was used to observe the scoring criteria for withdrawal symptoms.Morris space exploration method was used to observe the effects of UCN on study-memory.The multi-tube microiontophoresis method was used to observe the effects of UCN on NAc neuron’s spontaneous discharge changing manner.Also,the inhibitory effects of UCN on DA neuron’s cluster spontaneous discharging were tested,UCN2 and DA were identified on the same NAc neuron.In addition,the ELISA method was used to investigate the effects of UCN on tyrosine hydroxylase(TH)level in rats with morphine addiction.Results UCN improved the withdrawal symptoms of morphine addiction(P<0.05);UCN-L and UCN-H could significantly increase the percentage of total swimming time in the original platform quadrant(P<0.05);compared to the MCG group,the average discharge frequency of NAc neurons and the level of TH in the UCN-L and UCN-H groups decreased(P<0.05).Conclusions UCN improves morphine-addicted behavioral indicators and enhances learning and memory by reducing the level of TH in brain and inhibiting abnormal excitability of DA neurons in morphine-addicted rats.

关 键 词：伏隔核 吗啡成瘾 多巴胺能 微电泳 优洛克定 酪氨酸羟化酶 

分 类 号：R-332[医药卫生] R322.81