【摘要】 目的:探讨谷氨酸(Glu)对吗啡依赖大鼠戒断症状的影响及其作用机制。方法:建立大鼠吗啡依赖及戒断模型并给予评分,研究Glu对吗啡依赖大鼠戒断症状的影响;通过电生理,原位杂交,免疫组化方法研究丘脑束旁核神经元动作电位变化和c-fos基因表达的变化。结果:Glu剂量依赖性增加大鼠戒断症状的总评分(P<0.05);Glu使吗啡依赖大鼠丘脑束旁核的神经元自发放电和诱发放电频率增加(P<0.05),而诱发放电抑制时程缩短(P<0.05);在Glu诱发吗啡戒断过程中,c-fos基因表达水平显著增高(P<0.01,P<0.01)。结论:Glu可通过增加细胞电脉冲的形式兴奋神经元,提高依赖状态下神经元的兴奋性,加重吗啡依赖大鼠的戒断症状;Glu也可通过c-fos间接影响Glu受体和其他的神经递质的表达起作用。更多还原

【Abstract】 Objective: To investigate the effects and mechanisms of glutamate (Glu )on the process of morphine withdrawal. Methods: Animal models of morphine dependence and withdrawal were established and scored;the action potential of nucleus parafascicularis(Pf) neurons and c-fos protein and mRNA was tested using electrophysiology,in situ hybridization and immunohistochemistry. Results: Glu increased the score of withdrawal symptoms in a dose-dependent manner,which was higher in morphine dependent rats than in control group (P<0.05). At the same time of withdrawal process, Glu increased the frequency of spontaneous discharge and evoked discharge of pain-excitation neurons and inhibitory duration of evoked discharge decreased (P<0.05). In morphine withdrawal models evoked by Glu, the level of c-fos mRNA and protein was obviously higher than that in the normal control group (P<0.01, P<0.01, respectively). Conclusion: In the process of morphine withdrawal, Glu may directly excite the neurons and increase the frequency of action potential which can aggravate the morphine withdrawal symptoms in morphine withdrawal rats. Furthermore, the expression of c-fos increased during morphine withdrawal may play its role in the way of affecting the expression of Glu receptor and/or the synthesis of other neurotransmitters.更多还原