Abstract

gamma-Aminobutyric acid (GABA)A is a major inhibitory neurotransmitter in the mammalian CNS. GABAA ergic synapse is also an important site of action for a variety of centrally acting drugs, including benzodiazepines and barbiturates. Several lines of electrophysiological, behavioral, and biochemical studies implicate GABAA ergic synapse in the actions of alcohol. In electrophysiological studies, alcohol has been reported to enhance GABA-mediated responses in cortical neurons, spinal cord and substantia nigra, albeit, negative results have also been reported. In behavioral studies, GABAmimetics enhance alcohol's effects on motor coordination, while GABA antagonists have the opposite effect. In drug-combination studies, subeffective doses of alcohol, in combination with subeffective doses of other GABAmimetics, potentiate each other's effect in several seizure models. In functional studies, alcohol has been reported to potentiate GABA receptor-mediated 36Cl-flux in microsacs, neurosynaptosomes, and cultured spinal cord neurons at pharmacologically relevant concentrations. The potentiating effect of alcohol is blocked by GABA antagonists and the inverse agonists of the benzodiazepine receptor site. Taken together, these studies indicate that some of the central effects of alcohol are mediated via facilitation of GABAAergic transmission.