帕金森病大鼠伏隔核神经元电活动变化及5-HT7受体激活的作用

摘要

目的：研究帕金森病(Parkinson disease,PD)模型大鼠伏隔核(nucleus accumbens,NAc)神经元的电活动变化,以及 NAc 神经元对5-HT7受体刺激的反应。方法采用在体神经电生理学和神经药理学相结合的方法,观察 PD 大鼠 NAc 神经元的电活动变化以及 NAc 神经元对5-HT7受体激动剂的反应,并与假手术组进行对比分析。结果①PD 组大鼠 NAc 神经元的平均放电频率(5.46±0.88)Hz 显著高于假手术组(3.77±0.48)Hz(P <0.05)。PD 组大鼠65%的 NAc 神经元表现为爆发式放电、35%呈不规则放电；假手术组57.5%的 NAc 神经元呈爆发式放电、42.5%为不规则放电。与假手术组相比,PD 组大鼠 NAc 神经元的爆发式放电比例增多,但差异无统计学意义(P >0.05)。②体循环给予5-HT7受体激动剂 AS19后,假手术组大鼠的 NAc 神经元电活动变化整体上呈现兴奋反应,当累积剂量为160μg/kg 时,NAc 神经元的兴奋程度明显高于基础放电,且具有统计学意义(P <0.05)；PD 组大鼠虽然也表现为兴奋反应,但 NAc 神经元的兴奋效应在80μg/kg 累积剂量时具有统计学意义(P <0.05),PD 组产生统计学意义的累积剂量低于假手术组。AS19所引起的效应能够被特异性5-HT7受体拮抗剂 SB269970所反转。结论NAc 神经元5-HT7受体可能介导 PD 模型大鼠 NAc 神经元电活动增强效应。%Objective To investigate changes in the firing activities of nucleus accumbens (NAc)neurons and their response to 5-HT7 receptor stimulation in a rat model of Parkinson’s disease (PD).Methods The firing activities and response of NAc neurons to 5-HT7 receptor agonist in PD rats were recorded by in vivo electroneurophysiology and neuropharmacology and then were compared with those in the sham group.Results The mean firing rate of NAc neurons was (5.46 ±0.88)Hz in the sham rats and (3.77 ±0.48)Hz in the PD rats. The firing rate of NAc neurons increased significantly compared with that in the sham rats (P <0.05).In PD rats, 65% of NAc neurons fired in bursts and 35% fired irregularly.However,in the sham rats,57.5% of NAc neurons fired in bursts and 42.5% fired irregularly.There was no significant difference in the firing pattern of NAc neurons between the PD and sham rats (P >0.05 ).Systemic administration of 5-HT7 receptor agonist AS1 9 increased the firing rate of NAc neurons in the sham and PD rats.This excitation was significant at a high dose of 1 60 μg/kg for NAc neurons in the sham rats (P <0.05).However,the excitation produced by AS1 9 was significant at a high dose of 80 μg/kg in PD rats (P <0.05).The cumulative dose-produced excitation in the PD rats was lower than that in the sham rats.The effects induced by AS1 9 were reversed by the 5-HT7 receptor antagonist SB269970 in both groups.Conclusion The reinforced firing activity of NAc neurons might be mediated by 5-HT7 receptor in the neurons of PD rats.