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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 regulatory effect of 5-hydroxytryptamine-7 (5-HT7) receptor on 5-HT neurons in the dorsal raphe nucleus (DRN) of normal and Parkinson’s disease (PD) The properties of 5-HT7 receptor and the changes of this receptor trait in PD state were elucidated. Methods: Twenty-eight male SD rats were randomly divided into sham operation group (n = 12) and PD group (n = 16). Rats in PD group were injected 6-OHDA into the substantia nigra pars compacta, and sham-operated rats were injected with the same dose of saline. After intravenous injection of multiple doses (40 ~ 640μg · kg-1, iv) of 5-HT7 receptor agonist AS19 in two groups, we observed the discharge frequency of 5-HT neurons in rat DRN by extracellular electrophysiological recording After intravenous injection of 5-HT7 receptor antagonist SB269970, the sensitivity of PD rats to agonists and antagonists was observed and compared with sham operation group. Results: Compared with the basal discharge frequency, 5-HT7 receptor agonist AS19 (40-640μg · kg-1, iv) could significantly increase the discharge frequency and discharge frequency of 5-HT neurons Increased to 2.35 ± 0.16 (P <0.01). This effect could be completely reversed by SB269970 (200μg · kg-1, iv) and the discharge rate of rat 5-HT neurons was restored to 0.37 ± 0.03. In PD group, the same dose of AS19 (40 ~ 640μg · kg-1, i.v.) had no excitement effect on the discharge frequency of 5-HT neurons (P = 0.218). CONCLUSION: 5-HT7 receptor attenuates 5-HT neurons in dorsal raphe nucleus in PD model rats.