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Title: Effects of chronic ethanol administration on [3H]zolpidem binding in rat brain.

Authors: Devaud, L L; Morrow, A L

Published In Eur J Pharmacol, (1994 Apr 15)

Abstract: 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.

PubMed ID: 8050485 Exiting the NIEHS site

MeSH Terms: Animals; Brain Chemistry/drug effects*; Cerebellum/drug effects; Cerebellum/metabolism; Cerebral Cortex/drug effects; Cerebral Cortex/metabolism; Ethanol/pharmacology*; Hypnotics and Sedatives/pharmacokinetics*; In Vitro Techniques; Male; Pyridines/pharmacokinetics*; RNA, Messenger/biosynthesis; Rats; Rats, Sprague-Dawley; Receptors, GABA-A/drug effects; Receptors, GABA-A/metabolism; Zolpidem

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