Alcohol modulation of benzodiazepine receptors

The effects of ethanol-feeding and in vitro ethanol addition on the binding of ³H-diazepam and ³H-flunitrazepam in synaptosomal membrane preparations from rat cerebral cortex were investigated. Long-term ethanol-feeding (liquid-diet, 14 g/kg/day, pair-feeding, 35 days) significantly increased the diazepam dissociation constant (from 3.80 to 4.62 nM at 4°C and from 29.3 to 35.2 nM at 37°C). Similarly, the flunitrazepam dissociation constant was also increased (from 0.80 to 0.98 nM at 4°C and from 6.52 to 8.90 nM at 37°C). However, there was no significant difference in the number of receptors after ethanol feeding. γ-Aminobutyric acid (GABA) and pentobarbital increased the binding affinity by the same magnitude in control and ethanol-fed rats. Alcohol, in vitro (100 mM), did not have a significant effect on the binding parameters under most conditions. These findings suggest that long-term ethanol-feeding reduced the binding affinity of benzodiazepines without alteration of other properties of the receptors or their number.