ARE GABA-B RECEPTORS INVOLVED IN THE PHARMACOLOGICAL EFFECTS OF ETHANOL

The interaction of ethanol with GABAB-receptor system and the selectivity of phaclofen for GABA-receptor subtypes were investigated by employing an in vitro model of 36Cl-influx assay in mammalian cultured neurons and also in vivo models of picrotoxin- and NMDA-induced convulsions in rats. Ethanol (20 mM), without having any effect per se, potentiated the effect of GABA on 36Cl-influx, whereas at concentration 50 mM, ethanol activated Cl--channels directly in mice spinal cord cultured neurons. In contrast, (-)baclofen (100 μM) did not modify the effects of GABA or ethanol on 36Cl-influx. Similarly, phaclofen (500 μM), as well as pertussis toxin (140 ng/ml, overnight incubation) did not modify these effects. Interestingly, phaclofen (200 μg i.c.v.) reversed the anticonvulsant effect of ethanol, but not that of pentobarbital or diazepam or progabide, against picrotoxin-induced convulsions in rats. However, phaclofen failed to modify the anticonvulsant effect of ethanol against NMDA-induced convulsions. These observations indicate that phaclofen is devoid of GABAA-receptor blockade property, and the anticonvulsant effect of ethanol against picrotoxin may be mediated through the activation of both GABA-receptor subtypes. © 1990.