Electrophysiological interactions of ethanol with GABAergic mechanisms in the rat cerebellum in vivo.

Abstract

Biochemical studies indicate that ethanol (EtOH) will facilitate the activation of the GABAA/Cl- channel, and behavioral studies demonstrate that EtOH-induced sedative and incoordinating effects can be potentiated by GABA mimetics and blocked by GABA antagonists. It has been difficult, however, to demonstrate an EtOH-induced potentiation of the depressant electrophysiological effects of locally applied GABA in mammalian brain in vivo. Similarly, in this study, local EtOH applications only infrequently caused potentiations of the depressant effects of microiontophoretically 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 GABAA receptor antagonist bicuculline reversibly and apparently competitively blocked the depressant effects of locally applied EtOH on single cerebellar Purkinje neurons. Our data suggest that EtOH potentiation of GABA responses alone is insufficient to account for EtOH-induced depressions of cerebellar Purkinje neurons. However, these data clearly imply that activation of a GABAA receptor is required for the expression of EtOH-induced depressions of neuronal activity in this brain area. It is less clear how lower, nondepressant doses of EtOH interact with GABA mechanisms. We hypothesize that either the GABAA receptor mechanism must be sensitized to the potentiative effects of EtOH through the influences of neuromodulatory and/or hormonal regulation, or that EtOH interacts directly with these regulatory processes.