GABA/benzodiazepine receptor/chloride ionophore complex in brains of rat lines selectively bred for differences in ethanol-induced motor impairment.
In vitro ligand binding studies were used to compare GABA/benzodiazepine receptor/chloride ionophore complexes in various brain regions of ethanol-sensitive ANT and ethanol-insensitive AT rats. In naive rats, there were several, but fairly small line differences in the binding parameters of [3H]muscimol and [3H]flunitrazepam to cerebral cortical, cerebellar or hippocampal membranes washed with or without a detergent. GABA-stimulation of flunitrazepam binding in the cerebral cortex membranes was slightly greater in the AT than ANT rats. In detergent solubilized receptors, the GABA-stimulation of flunitrazepam binding emerged only in the presence of ethanol in most AT samples, whereas the GABA-stimulation was always observed in ANT samples and ethanol had no further effect. Pharmacological characteristics of [3H]t-butylbicycloorthobenzoate binding displaceable by picrotoxin were similar in both lines. Chronic ethanol administration tended to increase the number of these binding sites in the cerebral cortex of AT rats and to decrease them in the ANT rats. Although many differences between the lines were observed, our results indicate that the ethanol-sensitivity difference between the AT and ANT rat lines cannot be explained by enhanced function of the GABA/benzodiazepine receptor/chloride ionophore complex as far as this is revealed by in vitro binding studies. It remains to be studied whether these lines differ in presynaptic GABAergic mechanisms or in the actual function of the postsynaptic chloride channels before the role of GABA can be more accurately assessed in this genetic model for ethanol-induced motor impairment.
Malminen
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University of Tampere, Department of Biomedical Sciences, Finland.
Korpi
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D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005445:Flunitrazepam / Q000493:pharmacokinetics; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009048:Motor Skills / Q000187:drug effects*; D009118:Muscimol / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D007473:Ion Channels; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; C046308:tert-butylbicyclo-2-benzoate