苍白球P物质对帕金森病僵直模型大鼠的影响

目的 观察苍白球P物质对氟哌啶醇帕金森病僵直模型大鼠的影响.方法 行为学实验采用大鼠腹腔注射氟哌啶醇诱发帕金森病僵直模犁,苍白球分别微量注射生理盐水、NK-1受体激动剂SMSP、NK-1受体阻断剂SR140333B、SR140333B和SMSP的混合物,观察其对大鼠爬杆行为的影响.电生理学实验利用细胞外微压力注射上述药物,观察对苍白球神经元放电的影响.结果 大鼠腹腔注射氟哌啶醇可立刻产生僵直症状,平均僵直潜伏期最大值出现在第30分钟,为(259.8±34.8)s.最小值出现在第50分钟,为(145.2±54.8)s.双侧苍白球微量注射SMSP町明显改善僵直症状,第10分钟平均僵直潜伏期为(10.4±3.4)s,第60分钟为(58.4±38.8)s,差异有统计学意义(P＜0.01).双侧苍白球同时注入SR140333B和SMSP混合物可明显阻断SMSP的抗僵直症状,第10分钟为(176.4±64.4)s,第60分钟为(139.2±59.7)s,与单纯注射SMSP相比,差异有统计学意义(P＜0.01).进一步细胞外电生理记录结果 显示SMSP可使氟哌啶醇大鼠苍白球神经元放电频率由(13.4±4.2)Hz增加至(17.5±5.6)Hz,平均升高(29.4±8.6)%(P＜0.05,n=13),该效应可被SR140333B完全阻断(SR140333B:(10.3±2.5)Hz,SR140333B+SMSP:(11.3±3.0)Hz,P＞0.05,n=8).结论 苍白球P物质通过增加神经元放电,改善氟哌啶醇所致的神经元兴奋性降低,从而解除基底神经节对丘脑及大脑皮层的抑制效应,提示其可能起抗帕金森病的作用.

Effects of substance P in globus pallidus on haloperidol-induced Parkinsonian model rats

To investigate the effects of substance P in globus pallidus on haloperidol-induced Parkinson's disease model rat.Methods In behavioral experiments,guide cannulae constructed from stainless steel were implanted into the globus pallidus.After five days recovery,0.5 μl drugs(normal saline,SMSP,SR140333B,SR140333B + SMSP)were bilaterally microinjected into the globus pallidus in awake rats with haloperidol administration intraperitoneally.The catalepsy was then observed within 60 min.In electrophysiological study,an in vivo extracellular recording was performed to observe the effects of substance P on the firing rate of pallidal neurons.Resuits Haloperidol induced catalepsy in rats with intrapallidal saline microinjection.The maximum average latency was(259.8±34.8)s at the time point of 30th min.The minimum average latency was(145.2±54.8)s at 50th min.Bilateral microinjection of SMSP into globus pallidus significantly attenuated haloperidol-induced catalepsy (The average latency was(10.4±3.4)s at lOth rain and(58.4±38.8)s at 60th min,P＜0.01).This anticataleptic effect was completely counteracted by selective NK-1 receptors antagonist SR140333B(The average latency was(176.4±64.4)s at 10th min and(139.2±59.7)s at 60th rain,P＜0.01).Furthermore,micropressure ejection of SMSP significantly increased the firing rate of pallidal neurons(Basal:(13.4±4.2)Hz,SMSP:(17.5±5.6)Hz).The average increase was(29.4±8.6)%(P＜0.05,n=13).SR140333 B completely blocked SMSPinduced increase in firing rate(SR140333B:(10.3±2.5)Hz,SR140333 B + SMSP:(11.3±3.0)Hz,P＞0.05,n=8).Conclusion Based on the action of substance P in globus pallidus of parkinsonian rats,it is we hypothesized that activation of substance P receptor in globus pallidus may play a role in the treatment of Parkinson's disease.