THE ROLE OF GABA(A) RECEPTORS IN THE SUBSENSITIVITY OF PURKINJE NEURONS TO GABA IN GENETIC EPILEPSY-PRONE RATS

The GABA receptor subtype mediating responses of cerebellar Purkinje n eurons to the neurotransmitter was evaluated and compared in GEPR-9 vs . nonepileptic, genetic control GEPR-NE rats. Quantitative analysis of responses to microiontophoretically applied GABA, muscimol and baclof en indicated that the inhibitory action of GABA on cerebellar Purkinje neurons was mediated by GABA(A) receptors since muscimol produced res ponses similar to those of GABA and baclofen was without substantial e lectrophysiological action. In addition, Purkinje neurons in GEPR-9 an imals showed a similar reduced sensitivity to both GABA and muscimol. Radioligand binding studies using the GABA(A) receptor selective ligan d, [H-3]muscimol, and the benzodiazepine receptor selective ligand, [H -3]flunitrazepam, were conducted on cerebellar and cortical homogenate s from GEPR 9, GEPR-NE and Sprague-Dawley rats. No differences in the K-d or B-max for these ligands among the three groups studied were obs erved. The lack of significant changes in the K-d and B-max for these two ligands in the cerebellum suggests that the mechanism for the obse rved subsensitivity to GABA in the GEPR 9 rat lies beyond the level of the receptor, perhaps at the signal transduction process for GABA med iated inhibitory responses.