title: Alcohol and the GABA receptor-chloride channel complex of brain.
abstract: Several lines of research suggest that the depressant effects of intoxicant-anesthetic compounds are mediated through the GABA receptor-chloride ionophore. We have recently demonstrated a procedure that allows direct measurement of GABA-mediated chloride influx in neural tissue. Using this approach in conjunction with receptor-binding techniques, we examined the role of the GABAergic system using mice selected for genetic differences in ethanol hypnosis. A low concentration of ethanol (15 mM) enhanced the muscimol-stimulated chloride influx in cerebellar membranes from Long-sleep (LS-ethanol sensitive) mice, but had no effect on membranes from Short-sleep (SS-ethanol resistant) mice. In addition, muscimol was more potent in stimulating chloride flux and in inhibiting 35S-TBPS binding in LS membranes than in SS membranes. Mice from a heterogeneous stock were selected for differences in ethanol-induced loss of righting reflex. Cerebellar membranes from these mice also showed differences in ethanol augmentation of muscimol-stimulated chloride flux in vitro that were related to their differential sensitivity to ethanol in vivo. This combined genetic-neurochemical approach provides strong evidence for the importance of GABA-operated chloride channels in ethanol intoxication.
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*
chemical_list: D002712:Chlorides; D007473:Ion Channels; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol