The involvement of α₂-adrenoceptors in the anticonvulsive effect of swim stress in mice

Abstract.

Rationale: Various studies have shown that stressful manipulations in rats and mice lower the convulsant potency of GABA-related, but also some GABA-unrelated convulsants. The mechanism of this anticonvulsive effect of stress is still unknown. Objectives: We tested the possible involvement of α₂-adrenoceptors in the previously observed anticonvulsive effect of swim stress. Methods: The mice were, prior to exposure to swim stress and the IV infusion of picrotoxin, pre-treated with clonidine (an α₂-adrenoceptor agonist), yohimbine (a non-selective α₂-adrenoceptor antagonist), idazoxan (a selective α₂-adrenoceptor antagonist), or niguldipine (an α₁-adrenoceptor antagonist), and the latency to the onset of two convulsant signs was registered. Results: In control unstressed animals clonidine (0.1 and 1 mg/kg IP), yohimbine (2 mg/kg IP) and idazoxan (1 mg/kg IP) failed to affect the doses of picrotoxin needed to produce convulsant signs, while niguldipine (5 mg/kg IP) prolonged the latency, i.e. it enhanced the doses of picrotoxin producing running/bouncing clonus and tonic hindlimb extension. In swim stressed mice clonidine enhanced, while idazoxan decreased doses of picrotoxin needed to produce two convulsive signs. Yohimbine decreased the dose of convulsant needed to produce tonic hindlimb extension, while niguldipine enhanced doses of picrotoxin needed to produce both symptoms. Conclusions: The results demonstrate the α₂-adrenoceptor agonist-induced potentiation and α₂-adrenoceptor antagonist-induced diminution of the anticonvulsive effect of stress. Additionally, they show the anticonvulsive effect of niguldipine in unstressed and stressed animals. Hence, the results suggest that α₂-adrenoceptors are involved in the anticonvulsive effect of swim stress in mice.