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

Abstract

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. Key words: Globus pallidus; Substance P; Haloperidol; Parkinson's disease