title: Functional properties of GABAA receptors in two rat lines selected for high and low alcohol sensitivity.
abstract: The effects of lorazepam and sodium barbital on GABAA receptor function were evaluated in rat lines selected for differential sensitivity to the motor-impairing effects of ethanol [alcohol-insensitive (AT) and alcohol-sensitive (ANT) lines]. The effect of GABA on [3H]flunitrazepam and [3H]Ro 15-4513 binding and the effects of lorazepam and sodium barbital on [3H]muscimol binding were measured in cerebellar, cerebrocortical, and hippocampal membrane preparations. The effects of lorazepam and sodium barbital on muscimol-stimulated 36Cl- influx were measured using membrane vesicle suspensions from the same brain areas. No differences were found between the rat lines in the GABA-induced stimulation of [3H]flunitrazepam binding or in the lorazepam and sodium barbital-induced enhancement of either [3]muscimol binding or muscimol-stimulated 36Cl- flux. Neither was desensitization of the 36Cl- flux affected differently by ethanol, lorazepam, and barbital in vitro between the lines. The affinity of cerebellar diazepam-insensitive (DZ-IS) [3H]Ro 15-4513-binding sites for benzodiazepine agonists has been shown to be much greater in the ANT than the AT rats. In the present study, at 0 degrees C, GABA decreased [3H]Ro 15-4513 binding in the presence of diazepam only in ANT rats. Similarly, GABA decreased this binding at 37 degrees C in ANT rats having a high affinity for diazepam, whereas it enhanced the binding in all AT samples in those ANT samples where diazepam had a poor AT-like affinity. The decrease in binding in ANT samples is apparently caused by the enhancing effect of GABA on diazepam binding to DZ-IS [3H]Ro 15-4513-binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biomedical Sciences, University of Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Uusi-Oukari
authors.forename: E R
authors.initials: ER
authors.lastname: Korpi
mesh_terms: D000818:Animals; D001386:Azides / Q000378:metabolism; D001462:Barbital / Q000494:pharmacology; D001569:Benzodiazepines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004351:Drug Resistance; D000431:Ethanol / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism; D008140:Lorazepam / Q000494:pharmacology; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D001386:Azides; D002712:Chlorides; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D009118:Muscimol; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D001462:Barbital; D005445:Flunitrazepam; C042957:Ro 15-4513; D008140:Lorazepam