| The globus pallidus is becoming increasingly thought of as the central integrator of basal ganglia neurotransmission.By innervating all the basal ganglia nuclei,the globus pallidus plays an important role in normal movement regulation.5-hydroxytryptamine (5-HT) was discovered in the mammalian central nervous system in 1950s.An enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a bewildering diversity of behavioral and other physiological processes.Morphological studies have revealed that the globus pallidus receives abundant serotonergic innervations from raphe nuclei.Furthermore,both pre- and postsynaptic membrane of pallidal neurons expresses several 5-HT receptor subtypes.Object:To study the effects of 5-HT on the firing rate of globus pallidus neurons in normal and parkinsonian rats and behavioral effects of 5-HT on rotational behavior in parkinsonian rats.Methods:In vivo extracellular single unit recordings,6-hydroxydopamine(6-OHDA) lesion and cannulae embedding were used in the present study.Results:1.Micropressure ejection of 0.1 mM 5-HT predominantly produced excitation on globus pallidus neurons.In 21 out of 42 (50.0%) pallidal neurons,0.1 mM 5-HT increased the firing rate from 14.8±2.1 Hz to 19.6±2.5 Hz(P＜0.001).The average increase was 38.6±6.2%with regard to basal values. In four neurons(9.5%),5-HT decreased the spontaneous firing rate by 30.8±4.1%.The average basal firing rate of these neurons was 10.8±4.9 Hz.2.In 6-OHDA lesioned rats, micro-pressure ejection of 0.1mM 5-HT increased the spontaneous firing rate of 16 out of 37(43.2%) pallidal neurons from 10.3±1.1 Hz to 13.7±1.4 Hz(P＜0.001),The average increase was 35.7±4.1%.In 10 neurons(27.0%),5-HT decreased the spontaneous firing rate from 14.0±3.4 Hz to 8.5±2.4 Hz(P＜0.01),The average decrease was 40.6±5.7%.The reaction rate of the inhibitory effects of 5-HT on pallidal neurons increased on the lesioned side ofparkinsonian rats(P＜0.05 compared to normal).3.On the unlesioned side, micro-pressure ejection of 5-HT(0.1 mM) increased the firing rate of 25 out of 41(61.0%) pallidal neurons from 13.4±1.6 Hz to 18.3±2.0 Hz(P＜0.001).The average increase was 40.8±4.9%.5-HT also inhibited 4(9.8%) pallidal neurons by 42.5±12.5%.The reaction rate of the inhibitory effects decreased compared with that of the lesioned side(P＜0.05). There was no difference in the reaction rate of inhibitory effects between the unlesioned side and normal rats.4.In behaving rats,intrapallidal microinjection of 5-HT(0.1mM) alone did not induce any motor behavior or postural asymmetry in the unilaterally 6-OHDA-lesioned rats.However,when infused concomitantly with a subthreshold dose of 3,4-dihydroxyphenylalanine(L-DOPA,3 mg/kg i.p.),which can induce modest contralateral rotational behavior(31.0±14.7 r/h),5-HT significantly potentiated the number of contralateral rotations(189.0±58.6 r/h).Conclusion:Our in vivo electrophysiological study suggests that 5-HT mainly produces excitatory effects on globus pallidus neurons.Behavioral study further indicates that intrapallidal infusion of 5-HT potentiates L-DOPA-induced rotational behavior in 6-OHDA induced parkinsonian rats.The present findings may provide a rationale for further investigations into the potential of pallidal 5-HT system in the adjunctive therapy of Parkinson's disease.
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