title: Differences in GABA activity between ethanol withdrawal seizure prone and resistant mice.
abstract: Withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) lines of mice have been genetically selected based on the severity of handling-induced convulsions after identical chronic ethanol exposure. The present experiments showed that naive WSP mice were more sensitive than WSR mice to a subconvulsant dose of picrotoxin, bicuculline or pentylenetetrazole as measured by the ability of these drugs to exacerbate handling-induced convulsions. This may reflect a difference between lines in the GABA-chloride channel. The density and affinity of [35S]t-butylbicyclophosphorothionate (TBPS) binding sites, a cage convulsant which binds to the picrotoxin site on the GABA-chloride channel, was measured in the frontal cortex, remainder of the cortex, cerebellum and hippocampus. The binding properties of [3H]flunitrazepam and the potency of gamma-aminobutyric acid (GABA) to enhance flunitrazepam binding was characterized in whole brain samples. There were no differences between lines. The behavioral results suggest a role for the GABA-chloride channel in the differential ethanol withdrawal seizure behavior of WSR and WSP mice, but this is not due to changes in receptor densities or affinities.
authors.affiliation: Research Service, VA Medical Center, Portland, OR 97201.
authors.forename: D J
authors.initials: DJ
authors.lastname: Feller
authors.forename: R A
authors.initials: RA
authors.lastname: Harris
authors.forename: J C
authors.initials: JC
authors.lastname: Crabbe
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001640:Bicuculline; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003292:Convulsants; D000431:Ethanol; D005445:Flunitrazepam; D010433:Pentylenetetrazole; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate