ELECTROPHYSIOLOGICAL INTERACTIONS OF ETHANOL WITH GABAERGIC MECHANISMS IN THE RAT CEREBELLUM INVIVO

Biochemical studies indicate that ethanol (EtOH) will facilitate the a ctivation of the GABA(A)/Cl- channel, and behavioral studies demonstra te that EtOH-induced sedative and incoordinating effects can be potent iated by GABA mimetics and blocked by GABA antagonists. It has been di fficult, however, to demonstrate an EtOH-induced potentiation of the d epressant electrophysiological effects of locally applied GABA in mamm alian brain in vivo. Similarly, in this study, local EtOH applications only infrequently caused potentiations of the depressant effects of m icroiontophoretically applied GABA on cerebellar Purkinje neurons, and this interaction was modest when present. The predominant interaction of locally applied EtOH was an antagonism of GABA-induced depressions of neuronal activity. However, the GABA(A) receptor antagonist bicucu lline reversibly and apparently competitively blocked the depressant e ffects of locally applied EtOH on single cerebellar Purkinje neurons. Our data suggest that EtOH potentiation of GABA responses alone is ins ufficient to account for EtOH-induced depressions of cerebellar Purkin je neurons. However, these data clearly imply that activation of a GAB A(A) receptor is required for the expression of EtOH-induced depressio ns of neuronal activity in this brain area. It is less clear how lower , nondepressant doses of EtOH interact with GABA mechanisms. We hypoth esize that either the GABA(A) receptor mechanism must be sensitized to the potentiative effects of EtOH through the influences of neuromodul atory and/or hormonal regulation, or that EtOH interacts directly with these regulatory processes.