Swim stress selectively alters the specific binding of a benzodiazepine antagonist in mice.
The ability of flurazepam to antagonize the electrical precipitation of tonic hindlimb extension is reduced 24 h after mice are forced to swim for 10 min in cold water (6 degrees C). Presumably, this reduction in flurazepam's antiseizure efficacy reflects an environmental stress-induced modification of the GABAA receptor complex. The current study employed a variety of complementary in vitro approaches to characterize the delayed effects of cold-water swim stress on binding parameters of the GABAA receptor complex that may be associated with flurazepam's reduced antiseizure efficacy. The specific binding of [3H]flunitrazepam and the potentiation of this binding by chloride ions did not change after stress in the cerebral cortex, hippocampus, and cerebellum. Moreover, swim stress did not alter the ability of GABA to inhibit the binding of [35S]t-butylbicyclophosphorothionate (TBPS), a ligand that is a specific biochemical marker of the GABA-associated chloride ionophore, to crude membranes prepared from the cerebral cortex and cerebellum. Swim stress was associated with alterations of the specific binding of [3H]Ro 15-1788, a benzodiazepine receptor antagonist, to crude hippocampal and cerebellar membranes. The results are considered in the context of new insights derived from molecular cloning studies of the GABAA receptor complex.
Psychiatry Service, Department of Veterans Affairs, Medical Center, Washington, DC 20422.
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Park
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Hitri
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Lukacs
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Deutsch
D000818:Animals; D001921:Brain / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides / Q000378:metabolism; D005442:Flumazenil / Q000378:metabolism; D005479:Flurazepam / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D011963:Receptors, GABA-A / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*; D013550:Swimming; D014018:Tissue Distribution
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D011963:Receptors, GABA-A; D005442:Flumazenil; C037476:tert-butylbicyclophosphorothionate; D005479:Flurazepam