Effects of acute pentobarbital administration on GABAA receptor-regulated chloride uptake in rat brain synaptoneurosomes.
Effects of acute pentobarbital administration on GABAA receptor-regulated muscimol-stimulated, pentobarbital-stimulated, or flunitrazepam-enhanced, muscimol-stimulated chloride uptake were studied in the brains of Sprague-Dawley rats. Animals received sodium pentobarbital, 60 mg/kg IP, and cerebral cortical and cerebellar synaptoneurosomes were isolated at 10 min, 1 h, and when animals had awakened. The basal uptake of chloride was not changed in either cerebral cortex or cerebellum at different time periods after pentobarbital administration. Ten minutes after sodium pentobarbital administration, muscimol-stimulated chloride uptake was significantly reduced in cerebellum when the muscimol concentration was 2.5, 5, or 20 microM and in cerebral cortex when the concentration of muscimol was 5 or 10 microM (p less than 0.05, Duncan multiple-range test). One hour after pentobarbital administration or after animals had awakened, chloride uptake in brains from pentobarbital-treated animals was less at low concentration of muscimol (2.5 microM). No significant difference was found in either cerebral cortex or cerebellum in pentobarbital-(125-1,000 microM) stimulated or flunitrazepam-(2.5-20 microM) enhanced, muscimol-(3 microM) stimulated chloride uptake at different time periods after pentobarbital administration. Saline treatment had no effects on the basal or muscimol-stimulated chloride uptake in cerebellar synaptoneurosomes when compared with naive animals. The results demonstrate that GABAA receptor-regulated chloride uptake is decreased after acute pentobarbital administration, an effect that is reversible.
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
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D000818:Animals; D001921:Brain / Q000648:ultrastructure; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D005445:Flunitrazepam / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002712:Chlorides; D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; D010424:Pentobarbital