Differences in GABA activity between ethanol withdrawal seizure prone and resistant mice.
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.
Feller
D J
DJ
Research Service, VA Medical Center, Portland, OR 97201.
Harris
R A
RA
Crabbe
J C
JC
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*
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