The interactions of ethanol with the benzodiazepine-GABA receptor-ionophore complex

Ethanol, barbiturates and benzodiazepines have similar pharmacological effects. All of these drugs facilitate the inhibitory transmission mediated by GABA. Drugs that facilitate GABAergic transmission are effective in alleviating ethanol withdrawal symptoms. Acute ethanol administration increases the number of low affinity GABA receptor sites, while, during ethanol withdrawal, the affinity of this site is decreased. This decreased affinity during withdrawal correlated with the audiogenic seizure activity. These results indicate that in vivo ethanol interacts with GABA receptors, and this interaction may be responsible for some of the effects of ethanol and for some symptoms of withdrawal. Ethanol, like pentobarbital, also enhances [3H]diazepam binding to the Lubrol-solubilized membrane fraction in vitro. This effect was dose-related and was blocked by picrotoxinin and other GABA antagonists. Enhancement of [3H]diazepam binding by various alcohols did not correlate with lipid:water partition coefficients. Ethanol also partially inhibited the binding of [3H]-alpha-dihydropicrotoxinin in the Lubrol-solubilized fraction. These results indicate that ethanol, like pentobarbital, may modulate the benzodiazepine binding component of the benzodiazepine-GABA receptor-ionophore complex via the picrotoxinin site. The possible interpretation of these results, in relation to the GABAergic transmission, is discussed.