Beta-1 adrenoceptor antagonists potentiate the anticonvulsive effect of swim stress in mice.

To explore the possible involvement of beta adrenoceptor antagonists in the previously observed anticonvulsive effect of swim stress, the mice were, prior to administration of convulsants, pre-treated with propranolol (a non-selective beta adrenoceptor antagonist), betaxolol (a selective beta-1 adrenoreceptor antagonist), or ICI 118,551 (a selective beta-2 adrenoreceptor antagonist). In control unstressed animals, only propranolol [10 mg/kg, intraperitoneally (ip)] produced a significant change. It enhanced the threshold dose of picrotoxin producing tonic hindlimb extension. However, in swim-stressed animals, propranolol enhanced doses of picrotoxin producing tonic hindlimb extension and death, while betaxolol (20 mg/kg, i.p.) enhanced doses of picrotoxin producing running/bouncing clonus, tonic hindlimb extension and death. Pre-treatment with ICI 118,551 (4 mg/kg, i.p.) failed to affect doses of picrotoxin producing convulsions and death. The results demonstrate that blockade of beta-1 adrenoceptors potentiates the anticonvulsant effect of swim stress against convulsions produced by picrotoxin, a noncompetitive GABA(A) receptor antagonist.