Are GABAB receptors involved in the pharmacological effects of ethanol?

Abstract	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 microM) did not modify the effects of GABA or ethanol on 36Cl-influx. Similarly, phaclofen (500 microM), as well as pertussis toxin (140 ng/ml, overnight incubation) did not modify these effects. Interestingly, phaclofen (200 micrograms 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.
Authors	A K Mehta, M K Ticku
Journal	European journal of pharmacology (Eur J Pharmacol) Vol. 182 Issue 3 Pg. 473-80 (Jul 17 1990) ISSN: 0014-2999 [Print] Netherlands
PMID	2171947 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Radioisotopes Receptors, GABA-A phaclofen Picrotoxin progabide Ethanol Chlorine gamma-Aminobutyric Acid N-Methylaspartate Baclofen Diazepam
Topics	Animals Baclofen (analogs & derivatives, pharmacology) Cells, Cultured Chlorine Diazepam (pharmacology) Ethanol (pharmacology) Male Mice Mice, Inbred Strains N-Methylaspartate (pharmacology) Picrotoxin (pharmacology) Radioisotopes Rats Rats, Inbred Strains Receptors, GABA-A (drug effects) Seizures (chemically induced, physiopathology) Spinal Cord (cytology, drug effects) gamma-Aminobutyric Acid (analogs & derivatives, pharmacology)

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