Effects of serotonin and the 5-HT2/1C receptor agonist DOI on neurons of the cerebellar dentate/interpositus nuclei: possible involvement of a GABAergic interneuron.

The present study was designed to examine the effects of iontophoretically applied serotonin (5-HT) on neurons of the cerebellar dentate/interpositus nuclei in an in vitro slice preparation and to determine if the 5-HT2/1C receptor subtype could be responsible for mediating any effects noted with 5-HT. 5-HT and the 5-HT2/1C-selective agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) were iontophoretically applied alone and during superfusion of the 5-HT2/1C-selective antagonist, ritanserin. 5-HT and DOI elicited either inhibition or excitation of the spontaneous activity of dentate/interpositus neurons. An inhibitory response was induced by both compounds in the majority of cells responding. Ritanserin significantly attenuated the inhibitory response elicited by both 5-HT and DOI. In addition, the inhibitory response to DOI was significantly attenuated by the gamma-aminobutyric acid (GABA) antagonists, bicuculline and picrotoxin. Our results suggest that the 5-HT2/1C receptor subtype may be partially responsible for mediating 5-HT-induced inhibition of dentate/interpositus neurons, possibly via activation of GABAergic interneurons.