Ethanol exerts a dose-dependent stimulatory or inhibitory effect on the CNS; the mechanism of these effects is not, however, clear. Ethanol alters the action of several centrally acting GABA-ergic drugs, such as benzodiazepines and barbiturates, which suggests that ethanol interacts with GABA receptors. Ethanol exerts a biphasic effect on the binding of muscimol (GABA-A agonist) to GABA receptors in synaptosomal membranes obtained from different brain regions. Muscimol binding is inhibited at concentrations of ethanol ranging from 1.5 mM to 6 mM, whereas it is enhanced at higher concentrations. Decreased muscimol binding in the presence of low levels of ethanol was found to be due to reduced ligand affinity to the GABA receptors, whereas enhanced muscimol binding at high ethanol concentrations was due to increased receptor number. Glucocorticoids also appear to act directly on central GABA receptors, but in a dose-dependent manner opposite to that of ethanol. Nanomolar concentrations of glucocorticoids enhance muscimol binding, whereas micromolar concentrations inhibit binding. These effects are due to increased receptor affinity for the ligand and a decreased receptor number in the presence of low or high levels of glucocorticoids, respectively.
