| As a critical relay station in the indirect pathway of the basal ganglia,the globus pallidus occupies an important position in regulating normal movement function and participates the pathophysiological processes in several movement disorders.Being a monoamine neurotransmitter,5-hydroxytryptamine(5-HT) is not only involved in mediating many physiological functions,but also concerned with some central nerves system diseases.It is well known that the globus pallidus receives serotonergic innervation arising from raphe nuclei,mainly the dorsal raphe nucleus.A high 5-HT level and several kinds of 5-HT receptor subtypes were detected in the globus pallidus.A line of studies have revealed the close relationship between 5-HT system and Parkinson's disease.Object:To study the posturing regulation as well as the anticataleptic effects of 5-HT in globus pallidus on haloperidol-induced catalepsy,the effects of 5-HT on the firing rate of globus pallidus in rats treated with haloperidol,and the effects of brain 5-HT depletion on firing rate of globus pallidus in rats.Methods:Behavioral tests including turning behavioral tests and bar tests,in vivo extracellular single unit recordings,cannulae embedding and intra-nucleus or intra-cerebroventricular microinjection were used in present study.Results:1.In rats with haloperidol-induced catalepsy,unilateral microinjection of 5-HT into globus pallidus caused contralateral dystonic posturing. Within the range of concentration from 10 nM to 10 mM,5-HT induced a bell-shaped concentration-dependent contralateral dystonic posturing with the strongest effect at 10μM.The score of each 5-HT group was significantly higher than that of saline control group(P<0.01).2.In the bar tests,haloperidol administration produced a comparatively steady catalepsy state in rats.Bilateral microinjection of 5-HT(10μM) into globus pallidus significantly attenuated haloperidol-induced catalepsy with the total catalepsy time of 667.6±86.9 s compared with saline control group of 1253.0±103.1 s(P<0.01). This anticataleptic effect was completely counteracted by selective 5-HT1B receptors antagonist SB-224289,while partly reversed by selective 5-HT4 receptors antagonist GR-113808.In addition,the selective 5-HT7 receptors antagonist SB-269970 partly reversed the anticataleptic effect of 5-HT only at the incipient period after the intrapallidal injection.3.Micro-pressure injection of 0.1 mM 5-HT increased the spontaneous firing rate of globus pallidus in rats treated with haloperidol intraperitoneally.The average increase was 21.9±3.9%.In control group,normal saline only increased the firing rate by 3.9±2.3%.The difference between the two groups was significant(P<0.01).4.In 5-HT-depleted rats,induced by intra-cerebroventricular administration of 5,7-DHT,the average firing rate of 29 pallidal neurons recorded was 16.2±1.6 Hz.Another 28 pallidal neurons in rats of sham operation,treated with antiscorbic acid solution intra-cerebroventriculary,showed an average firing rate of 15.0±1.8 Hz.There was no significant difference between the two groups(P>0.05).Conclusion:The present behavioral study provides evidence that activation of 5-HT receptors within globus pallidus exerts an anticataleptic effect in rats.Multiple 5-HT receptors,5-HT1B,5-HT4 and 5-HT7 receptors,may be involved in the anticatalepsy.Our in vivo electrophysiological results suggest that the anticataleptic effect of 5-HT may be achieved by increasing the excitability of pallidal neurons.The present studies may provide a rational for further investigations into the potential of pallidal 5-HT system in prevention and cure of Parkinson's disease.
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