5-羟色胺-7受体激动剂对帕金森病模型大鼠内侧前额叶皮层锥体神经元兴奋性的影响  

Effect of 5-HT_7 receptor agonist on pyramidal neurons in the medial frontal cortex in a rat model of Parkinson's disease

作　　者：范玲玲[1] 邓博[1] 闫君宝[1] 胡志红[1] 任爱红[1] 胡咏梅[1] 杨东伟[1] 

机构地区：[1]河南科技大学医学院,河南洛阳471003

出　　处：《南方医科大学学报》2016年第6期756-762,共7页Journal of Southern Medical University

基　　金：河南省教育厅科学技术研究重点项目(14B180007);洛阳市科技发展计划项目(1401087A-5)

摘　　要：目的探讨5-羟色胺(5-hydroxytryptamine,5-HT)-7受体对帕金森病(Parkinson's disease,PD)模型大鼠内侧前额叶皮层(medial prefrontal cortex,m PFC)中锥体神经元兴奋性的影响。方法以正常大鼠和6-羟多巴胺单侧损毁黑质致密部建立的PD模型大鼠为研究对象,采用在体细胞外生物电记录的方法,观察5-HT7受体激动剂AS 19对m PFC中锥体神经元电活动的影响。结果无论是体循环还是局部给予AS 19都能引起正常大鼠m PFC锥体神经元呈现兴奋、抑制和不变3种形式的反应,而总体反应是兴奋,而且AS 19引起的抑制效应能被GABAA受体拮抗剂picrotoxinin反转。对于PD模型大鼠,AS 19全身给药也能使m PFC锥体神经元产生3种反应,总体反应是兴奋,但产生兴奋所需的药物累积剂量明显比正常大鼠高,且抑制效应只能被picrotoxinin部分反转,局部应用AS 19不改变模型鼠m PFC锥体神经元的放电。结论 m PFC锥体神经元的活动直接或间接地受到5-HT7受体的调控,而黑质-纹状体通路的变性会引起这些神经元对AS 19的反应性降低。Objective To investigate the activity of pyramidal neurons in the medial prefrontal cortex（m PFC） of normal and 6-OHDA- lesioned rats and the responses of the neurons to 5- hydroxytryptamine- 7（5- HT7） receptor stimulation. Methods The changes in spontaneous firing of the pyramidal neurons in the m PFC in response to 5-HT7 receptor stimulation were observed by extracellular recording in normal and 6- OHDA- lesioned rats. Results Both systemic and local administration of 5- HT7 receptor agonist AS 19 resulted in 3 response patterns（excitation, inhibition and no change） of the pyramidal neurons in the m PFC of normal and 6- OHDA- lesioned rats. In normal rats, the predominant response of the pyramidal neurons to AS 19 stimulation was excitatory, and the inhibitory effect of systemically administered AS 19 was reversed by GABAAreceptor antagonist picrotoxinin. In the lesioned rats, systemic administration of AS 19 also increased the mean firing rate of the pyramidal neurons, but the cumulative dose for producing excitation was higher than that in normal rats. Systemic administration of AS 19 produced an inhibitory effect in the lesioned rats, which was partially reversed by picrotoxinin. Local administration of AS 19 at the same dose did not change the firing rate of the neurons in the lesioned rats. Conclusion The activity of m PFC pyramidal neurons is directly or indirectly regulated by 5-HT7 receptor, and degeneration of the nigrostriatal pathway leads to decreased response of these neurons to AS 19.

关 键 词：帕金森病 内侧前额叶皮层 锥体神经元 5-羟色胺-7受体 大鼠 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]