Response of cerebellar Purkinje cells to serotonin and the 5-HT1A agonists 8-OH-DPAT and ipsapirone in vitro.
These studies were undertaken in an attempt to classify the receptor subtypes 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 in 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.
Darrow
E J
EJ
Department of Physiology, Texas Tech University Health Sciences Center, Lubbock 79430.
Strahlendorf
H K
HK
Strahlendorf
J C
JC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology*; D007478:Iontophoresis; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D009281:Naphthalenes; D011743:Pyrimidines; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D013134:Spiperone; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin