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帕金森病大鼠中缝背核5--羟色胺能神经元电活动的变化

张巧俊, 高蕊, 刘健, 刘娅萍, 王爽

西安交通大学医学院第二附属医院神经内科.陕西,西安 710004；西安交通大学医学院生理学与病理生理学系.陕西,西安 710061

摘要

该实验采用玻璃微电极细胞外记录法，观察了帕金森病(Parkinson's disease, PD)大鼠中缝背核(dorsal raphe nucleus, DRN) 5--羟色胺(5--hydroxytryptamine, 5--HT)能神经元(serotonergic neurons)电活动的变化。在大鼠右侧中脑黑质致密部内微量注射6--羟多巴胺(6-hydroxydopamine, 6--OHDA)制作PD模型。结果显示，对照组和PD组大鼠DRN中5--HT能神经元的放电频率分别是(1.76±0.11) Hz (n=24)和(2.43±0.17) Hz (n=21)，PD组大鼠的放电频率显著高于对照组({sl P}<0.001)。对照大鼠中，92% (22/24)的神经元呈现规则放电，8% (2/24)为爆发式放电；PD大鼠中，具有规则、不规则和爆发式放电的神经元比例分别为9% (2/21)、43% (9/21)和48% (10/21)，爆发式放电的5-HT能神经元比例明显高于对照组(P<0.001)。在正常大鼠中，DRN内局部注射5--HT_(1A)拮抗剂WAY--100635 (3 #mu#g/200 nL)显著增加5-HT能神经元的放电频率而不影响其放电形式({sl n}=19, {sl P}<0.002)；而WAY--100635不改变PD大鼠5--HT能神经元的放电频率和放电形式({sl n}=17, {sl P}>0.05)。结果提示，用6--OHDA损毁黑质致密部造成的PD模型大鼠中神经元5--HT1A受体功能失调，并且DRN参与PD的病理生理学机制。

关键词： 中缝背核; 5-HT_(1A)受体; WAY-100635; 帕金森病

Changes in the firing activity of serotonergic neurons in the dorsal raphe nucleus in a rat model of Parkinson's disease

Zhang Qiaojun, Gao Rui, Liu Jian, Liu Yaping, Wang Shuang

Department of Neurology, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University.Xi'an 710004,Shaanxi；China

Abstract

In the present study, changes in the neuronal activity of serotonergic neurons in the dorsal raphe nucleus (DRN) and the effect of the selective 5-HT_(1A) receptor antagonist WAY-100635 in a rat model of Parkinson's disease (PD) were investigated by using extracellular single unit recording. Rat model of PD was produced by microinjection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta on the right side of the brain. The results showed that the mean spontaneous firing rate of DRN serotonergic neurons in the control and 6-OHDA-lesioned rats were (1.76+0.11) spikes/s (n=24) and (2.43+0.17) spikes/s (n=21),respectively. The firing rate of serotonergic neurons in 6-OHDA-lesioned rats was significantly higher than that in the control rats (P＜0.001). In the control rats, 92% (22/24) of the neurons fired regularly and 8% (2/24) fired in bursts. In rats with 6-OHDA lesions, 9%(2/21) of neurons fired regularly, 43% (9/21) exhibited irregular pattern and 48% (10/21) fired in bursts. The percentage of DRN serotonergic neurons firing in bursts was obviously higher in 6-OHDA-lesioned rats than that in the control rats (P＜0.001). Local injection of WAY-100635 (3 μg in 200 nL) into the DRN significantly increased the firing rate of serotonergic neurons with no change in firing pattern in the control rats (n=19, P＜0.002), but did not change the firing rate and firing pattern of serotonergic neurons in 6-OHDA-lesioned rats (n=17, P＞0.05). These results suggest the dysfunction of 5-HT_(1A) receptor in 6-OHDA-lesioned rats and the involvement of the DRN in the pathophysiological mechanism of PD.

Key words: Dorsal raphe nucleus;5-HT_(1A) receptor;WAY-100635;Parkinson's disease

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引用本文：

张巧俊, 高蕊, 刘健, 刘娅萍, 王爽. 帕金森病大鼠中缝背核5--羟色胺能神经元电活动的变化[J]. 生理学报 2007; 59 (2): 183-189.

Zhang Qiaojun, Gao Rui, Liu Jian, Liu Yaping, Wang Shuang. Changes in the firing activity of serotonergic neurons in the dorsal raphe nucleus in a rat model of Parkinson's disease. Acta Physiol Sin 2007; 59 (2): 183-189 (in Chinese with English abstract).