5-HT_7受体对帕金森病模型大鼠中缝背核5-HT能神经元电活动的调控作用

Regulation effect of 5-HT_7 receptor on electrical activity of 5-HT neurons in nucleus raphes dorsalis of rats with Parkinson's disease

目的：探讨5-羟色胺-7（5-HT7）受体对正常和帕金森病（PD）模型大鼠中缝背核（DRN）5-羟色胺（5-HT）能神经元电活动的调控作用,阐明5-HT7受体的性质及PD状态下该受体性状的改变。方法：28只雄性SD大鼠随机分为假手术组（n=12）和PD组（n=16）。PD组大鼠黑质致密部内注射6-OHDA,假手术组大鼠注射同等剂量生理盐水。2组大鼠静脉注射多个剂量（40-640μg·kg^-1,i.v.）的5-HT7受体激动剂AS19后,采用体细胞外电生理学记录观察大鼠DRN中5-HT能神经元放电频率的变化;静脉注射5-HT7受体拮抗剂SB269970后,观察PD组大鼠对激动剂和拮抗剂的敏感性,并与假手术组进行比较。结果：在假手术组中,与基础放电频率比较,5-HT7受体激动剂AS19（40-640μg·kg^-1,i.v.）能够明显增加大鼠5-HT能神经元的放电频率,放电频率增加到2.35±0.16（P〈0.01）;这种作用可以被SB269970（200μg·kg^-1,i.v.）完全反转,使大鼠5-HT能神经元的放电率恢复为0.37±0.03。在PD组中,相同剂量AS19（40-640μg·kg^-1,i.v.）对5-HT神经元的放电频率无兴奋效应（P=0.218）。结论：5-HT7受体对PD模型大鼠中缝背核5-HT能神经元的调控作用减弱。

Objective To investigate the different effects of 5-hydroxytryptamine-7（5-HT7）on the electrical activities of 5-HT neurons in nucleus raphes dorsalis（DRN）of the normal and parkinson＇s disease（PD）rats,and to clarify the properties of 5-HT7 receptor and the changes in the PD rats.Methods 28 male SD rats were randomly divided into sham opration group（n=12）and PD group（n=16）.6-OHDA was injected in the subtantia nigra pars compacta（SNc）of the rats in PD group,and the same dose of normal saline was injected in the SNc of the rats in sham opration group.The rats in two groups were injected with different doses of（40-640μg·kg^-1,i.v.）5-HT7 receptor agonist AS19,and the changes of firing rates in 5-HT neurons of the rats were observed by extracellular electrophysiological recording in DRN.5-HT7 receptor antagonist SB269970 was injected to observe the sensitivities to agonist and the antagonist of the rats in PD group,and compared with sham operation group.Results Systemic administration of the selective 5-HT7 receptor agonist AS19（40-640μg·kg^-1,i.v.）increased the firing rate of 5-HT neurons of the rats in sham operation group,the mean firing rate of 5-HT neurons in the DRN was changed to 2.35±0.16（P〈0.001）,and completely reversed by the subsequent administration of SB269970（200μg·kg^-1,i.v.）,the mean firing rate of 5-HT neurons in the DRN was changed to 0.37±0.03.The same dose of AS19 had no affection in the rats in PD group（P=0.218）.Conclusion The regulation effect of5-HT7 receptor on the 5-HT neurons in DRN of the PD rats is decreased.