RESPONSE OF CEREBELLAR PURKINJE-CELLS TO SEROTONIN AND THE 5-HT1A AGONISTS 8-OH-DPAT AND IPSAPIRONE INVITRO

These studies were undertaken in an attempt to classify the receptor subtyps mediating the inhibitory effects of serotonin (5-HT) on cerebellar Purkinje cells in the in vitro slice preparation. 5-HT and the 5-HT1A specific agonists 8-hydroxy-2(di-n-propyl-amino)tetralin (8-OH-DPAT) and ipsapirone were iontophoretically applied to Purkinje cells during control periods and periods of concurrent application of the 5-HT1A/5-HT2 antagonist spiperone. 5-HT was found to produce three distinct effects on Purkinje cell spontaneous discharge: inhibition, excitation and a biphasic effect. Iontophoretically applied 8-OH-DPAT and ipsapirone elicited only inhibition of Purkinje cell firing all cells tested. Purkinje cell inhibitions elicited by 5-HT, 8-OH-DPAT and ipsapirone were all found to be significantly dose-dependent. However, while dose-response curves for 8-OH-DPAT and ipsapirone were found to be identical, they both differed significantly from the 5-HT curve. Spiperone was shown to significantly attenuate Purkinje cell inhibition induced by 5-HT, 8-OH-DPAT and ipsapirone. In several cells 5-HT-induced inhibition of spontaneous discharge was reversed to excitation in the presence of spiperone. This was never observed with either 8-OH-DPAT or ipsapirone. Thus, our results suggest that 5-HT-induced Purkinje cell inhibitions are at least partially mediated by the 5-HT1A receptor subtype, and there also may be additional 5-HT receptor subtypes present mediating other responses. Ultimate Purkinje cell responses to 5-HT may be due to summation of responses induced by activation of several 5-HT receptor subtypes. © 1990.