SWIM STRESS SELECTIVELY ALTERS THE SPECIFIC BINDING OF A BENZODIAZEPINE ANTAGONIST IN MICE

The ability of flurazepam to antagonize the electrical precipitation o f tonic hindlimb extension is reduced 24 h after mice are forced to sw im 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 GABA(A) receptor complex. The current stud y employed a variety of complementary in vitro approaches to character ize the delayed effects of cold-water swim stress on binding parameter s of the GABA(A) receptor complex that may be associated with flurazep am's reduced antiseizure efficacy. The specific binding of [H-3]flunit razepam and the potentiation of this binding by chloride ions did not change after stress in the cerebral cortex, hippocampus, and cerebellu m. Moreover, swim stress did not alter the ability of GABA to inhibit the binding of [S-35]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 ce rebellum. Swim stress was associated with alterations of the specific binding of [H-3]Ro 15-1788, a benzodiazepine receptor antagonist, to c rude hippocampal and cerebellar membranes. The results are considered in the context of new insights derived from molecular cloning studies of the GABA(A) receptor complex.