Modulatory Action of Serotonin on Glutamate-induced Excitation of Cerebellar Purkinje Cells

The effects of serotonin (5-hydroxytryptamine, 5-HT) on glutamate-induced excitation of Purkinje cells were examined. Pulsatile iontophoretic applications of glutamate (1-25 nA) induced consistent increases in the spontaneous activity of Purkinje cells. When serotonin was applied continuously with currents that elicited minimum changes in the spontaneous rate, it inhibited or blocked glutamate-induced excitations significantly in most Purkinje cells. We also examined the effects of high currents of serotonin on spontaneous activity of Purkinje cells. High currents of serotonin induced 3 different effects: inhibitions, biphasic effects comprising transient inhibition followed by excitation, and excitations. Nonetheless, whether it inhibited or excited the activity of Purkinje cells, serotonin inhibited glutamate-induced excitations consistently. The effect of a putative 5-HT antagonist methysergide (UML) was also examined. Methysergide consistently attenuated or antagonized the inhibitory effects of serotonin on glutamate-induced excitations. This finding suggests strongly that inhibitory effects of 5-HT on glutamate excitations observed in the present study is the specific action of serotonin.