Effects of chronic ethanol administration on [3H]zolpidem binding in rat brain.
The effect of chronic ethanol administration on [3H]zolpidem binding was measured in rat brain. [3H]Zolpidem selectively labels gamma-aminobutyric acidA-benzodiazepine type 1 receptors, which are highly correlated with ethanol-sensitive gamma-aminobutyric acid (GABA) responses in brain. Recombinant expression studies have suggested that this GABAA receptor subtype requires the expression of alpha 1 subunits and is not selectively labeled by classic GABAergic ligands. Since chronic ethanol administration reduces alpha 1 subunit mRNA and polypeptide levels, we investigated whether alterations in [3H]zolpidem binding would also be detected. Chronic ethanol administration did not reduce [3H]zolpidem binding. Instead small, but reproducible, increases in [3H]zolpidem binding density were detected in cortex and cerebellum with no change in affinity. No alterations in [3H]zolpidem binding to striatum and hippocampus were observed. These findings suggest that chronic ethanol administration may have differential effects on [3H]zolpidem binding sites and alpha 1 subunit expression. Alterations in alpha 1 subunit expression following chronic ethanol administration may involve other GABAA receptor subtypes or high affinity [3H]zolpidem binding may be dependent on the expression of additional GABAA receptor subunits.
Devaud
L L
LL
Department of Psychiatry and Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599-7175.
Morrow
A L
AL
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D000077334:Zolpidem
D006993:Hypnotics and Sedatives; D011725:Pyridines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D000431:Ethanol; D000077334:Zolpidem