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 degrees C and from 29.3 to 35.2 nM at 37 degrees C). Similarly, the flunitrazepam dissociation constant was also increased (from 0.80 to 0.98 nM at 4 degrees C and from 6.52 to 8.90 nM at 37 degrees C). However, there was no significant difference in the number of receptors after ethanol feeding. Gamma-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.
Rottenberg
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D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D003975:Diazepam / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism; D006801:Humans; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D010424:Pentobarbital; D003975:Diazepam