Decreased convulsant potency of picrotoxin and pentetrazol and enhanced [3H]flunitrazepam cortical binding following stressful manipulations in rats.

Various stressful manipulations in rats (cold-water swim, electric foot-shock administration, imparied access to food reward) were found to reduce the convulsant potency of drugs which interfere with GABA or benzodiazepine central processes. The convulsant threshold dosages of picrotoxin (0.4 mg/ml) or pentetrazol (10 mg/ml) administered after the stress by infusion (0.2 ml/min) via a vein of the tail were enhanced. The onset of generalized seizures induced by isoniazid (800 mg/kg) or by thiosemicarbazide (64 mg/kg) i.p. was delayed after cold-water swim. However, convulsant threshold dosages of bemegride or strychnine perfused at 2 and 0.2 mg/ml respectively were not changed by stress. Cold-water swim increased the number of cortical (but not cerebellar) [3H]flunitrazepam binding sites (+ 24%) but failed to alter cortical [3H]muscimol binding. This post-stress enhancement of binding sties, although suppressed by bicuculline (10(-4) M) seems not to be dependent on GABAergic mechanisms. Indeed cold-water stress did not reduce the ability of muscimol (10(-6) and 10(-5) M) and GABA (5 x 10(-6) and 5 x 10(-5) M) to increase flunitrazepam binding. Finally, this post-stress enhancement of benzodiazepine binding was not found to be paralleled by changes in the protective effects of diazepam against picrotoxin- or pentetrazol-induced seizures.