选择性5-HT1A受体拮抗剂WAY-100635增加6-羟多巴胺损毁大鼠杏仁基底外侧核的神经活动

本文采用玻璃微电极细胞外记录法,观察正常大鼠和6-羟多巴胺(6-hydroxydopamine,6-OHDA)损毁黑质致密部大鼠杏仁基底外侧核(basolateral nucleus,BL)神经元电活动的变化,以及体循环给予选择性5-HT1A受体拮抗剂WAY-100635对神经元电活动的影响.结果显示,正常大鼠BL投射神经元和中间神经元的放电频率分别足(O.39±0.04)Hz和(0.83±0.16)Hz,6-OHDA损毁大鼠BL投射神经元和中间神经元的放电频率分别足(0.32±0.04)Hz和(0.53±0.12)Hz,与正常大鼠相比无显著差异.在正常大鼠,所有投射神经元呈现爆发式放电;94%的中间神经元为爆发式放电,6%为不规则放电.在6.OHDA损毁大鼠,85%的投射神经元呈现爆发式放电,15%为不规则放电;86%的中间神经元为爆发式放电,14%为不规则放电,与正常大鼠相比无显著差别.静脉给予0.1 mg/kg体重的WAY-100635不改变正常大鼠和6-OHDA损毁人鼠BL投射神经元和中间神经元的放电频率.然而,0.5 mg/kg体重的WAY-100635却显著降低正常大鼠BL投射神经元的平均放电频率(P<0.01),明显增加6-OHDA损毁大鼠BL投射神经元的平均放电频率(P<0.004).高剂量WAY-100635不影响正常大鼠和6-OHDA损毁大鼠BL中间神经元的平均放电频率.结果表明,黑质多巴胺能损毁后内在和外在的传入调节BL神经元的活动,在正常大鼠和6-OHDA损毁大鼠5-HT1A 受体调节投射神经元的活动,并且在6-OHDA损毁大鼠WAY-100635诱发投射神经元平均放电频率增加.结果提示,5-HT1A 受体在帕金森病情感性症状的产生中起重要作用.

The selective 5-HT(1A) receptor antagonist WAY-100635 increases neuronal activity of the basolateral nucleus of the amygdala in 6-hydroxydopamine-lesioned rats

In the present study, extracellular recording was used to examine the neuronal activity of the basolateral nucleus (BL) of theamygdala and the effects of systemic administration of the selective 5-HT1A receptor antagonist WAY-100635 on the neuronal activityin the normal rats and rats with 6-hydroxydopamine (6-OHDA)-produced lesions in the substantia nigra pars compacta (SNc), Theresults showed that the firing rates of BL projection neurons and intemeurons were (0.39±0.04) Hz and (0.83±0.16) Hz in the normalrats, and (0.32±0.04) Hz and (0.53±0.12) Hz in 6-OHDA-lesioned rats. There was no significant difference in the firing rates of BLprojection neurons and interneurons between the normal and 6-OHDA-lesioned rats. In the normal rats, all BL projection neurons firedin burst; 94% of BL interneurons fired in burst and 6% fired irregularly. In 6-OHDA-lesioned rats, 85% of BL projection neurons displayed a burst fLdng pattern and 15% fired irregularly; 86% of BL intemeurons had a burst firing pattern and 14% fired irregularly.The distribution of firing patterns of projection neurons and interneurons in the BL in 6-OHDA-lesioned rats did not differ from thatin the normal rats. Systemic administration of WAY-100635 at 0.1 mg/kg body weight did not change the mean firing rates of projectionneurons and interneurons in the BL in both normal and 6-OHDA-lesioned rats, However, a higher dose of WAY-100635 at 0.5 mg/kgbody weight significantly decreased the mean firing rate of BL projection neurons from (0.43±0.07) to (0.15±0.02) Hz in the normalrats (P<0.01), but significantly increased the activity of BL projection neurons in 6-OHDA-lesioned rats from (0.37±0.08) to (0.69±0.18) Hz (P<0.004). The mean firing rates of BL interneurons in the normal and 6-OHDA-lesioned rats did not change after adminis-tration of a higher dose of WAY-100635 at 0.5 mg/kg body weight. These results demonstrate that the activity of BL neurons aftersubstantia nigra dopaminergic lesion in the SNc is regulated by activation of intrinsic and extrinsic inputs, and that 5-HT1A receptorssignificantly contribute to the regulation of the activity of BL projection neurons in both normal and 6-OHDA-lesioned rats. Furthermore,WAY-100635 induced an increase in the mean firing rate of projection neurons in the BL in 6-OHDA-lesioned rats, suggesting that5-HT1A receptor is likely to play a role in generating affective symptoms in Parkinson's disease.