The role of alpha2-adrenoceptors in the modulatory effects of morphine on seizure susceptibility in mice.

Abstract

To evaluate the effect of the alpha2-adrenoceptor agonist clonidine and the antagonist yohimbine on the dual modulation of seizure susceptibility induced by morphine and the anticonvulsant effect of acute stress in mice. The thresholds for the clonic seizures induced after intravenous administration of pentylenetetrazole (PTZ) or bicuculline were assessed in mice weighing 23-30 g. Acute stress was induced by restraining mice for 2 h in a restrainer. Morphine at lower doses (0.5, 1, and 3 mg/kg) increased and, at higher doses (15, 30, and 75 mg/kg), decreased the seizure threshold. Pretreatment with clonidine (0.001-0.1 mg/kg) inhibited the anticonvulsant effect of morphine, while potentiating its proconvulsant effect. Conversely, yohimbine (0.5-2 mg/kg) potentiated the anticonvulsant effect of morphine but inhibited its proconvulsant effects. Acute stress induced an anticonvulsant effect that was reversible by naloxone (1 mg/kg) or clonidine (0.05-0.1 mg/kg) or a combination of their lower doses (0.3 and 0.01 mg/kg, respectively), while being potentiated by yohimbine (1 mg/kg). alpha2-Adrenoceptors play a dual role in the anticonvulsant effects of morphine. The activation of these receptors also can decrease the anticonvulsant effect of acute restraint stress in mice.