8-BROMO-CAMP MIMICS BETA-ADRENERGIC SENSITIZATION OF GABA RESPONSES TO ETHANOL IN CEREBELLAR PURKINJE NEURONS IN-VIVO

Previous studies in our laboratory indicated that electrophysiological responses of cerebellar Purkinje neurons to GABA were not routinely p otentiated by ethanol (EtOH), and the potentiation was not large when it occurred. In the presence of beta-adrenergic agonists, such as isop roterenol, however, GABA inhibitions became sensitive to potentiation by EtOH in nearly every Purkinje neuron tested. beta-Adrenergic recept or activation alone also modulates (potentiates) GABA responses on Pur kinje neurons, and this has been reported to be mediated by a cAMP sec ond messenger system, Herein, we report that the membrane-permeable cA MP analog, 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP), bu t not the membrane-impermeable cAMP, can also modulate GABA responses and that EtOH potentiates this facilitatory action of 8-Br-cAMP. These effects are not likely caused by adenosine receptor mechanisms, becau se this 8-bromoadenosine mediated modulation and sensitization was obs erved in the presence of systemic theophylline. These data suggest tha t the beta-adrenergic modulation and sensitization to EtOH of cerebell ar Purkinje neuron GABA responses occur via a cAMP second messenger me chanism.