Picrotoxin but not bicuculline antagonizes 5-hydroxytryptamine-induced inhibition of cerebellar Purkinje neurons

Abstract

The inhibitory effects of iontophoretically applied serotonin (5-hydroxytryptamine) on Purkinje cells were examined in the presence of the GABA antagonists picrotoxin and bicuculline in vivo and in vitro cerebellar preparations. Continuous application of the GABA-mediated chloride ionophore antagonist, picrotoxin, at currents that induced significant antagonism of GABA-elicited inhibition of Purkinje cells decreased the inhibitory effects of serotonin significantly in the same neurons. Bicuculline, an antagonist of GABA receptors, exerted different actions on serotoninmediated inhibition of Purkinje cells. Continuous iontophoretic applications of bicuculline antagonized the inhibitory effects of GABA on Purkinje cells significantly, but failed to induce significant attenuation of serotonin-mediated inhibition. The inhibitory effects of serotonin on Purkinje cells were examined also in the presence of nipecotic acid, an inhibitor of GABA reuptake, and a low Ca 2-high Mg 2+ medium, which blocks synaptic transmission. Under these circumstances, serotonin-mediated inhibitions were not influenced significantly, indicating that its inhibitory effects do not involve release or reuptake of GABA. These results indicate that there might be a linkage between the actions of serotonin and GABA.