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The Role of α 2 ‐Adrenoceptors in the Modulatory Effects of Morphine on Seizure Susceptibility in Mice
Author(s) -
Homayoun Houman,
Khavandgar Simin,
Dehpour Ahmad Reza
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2002.49701.x
Subject(s) - yohimbine , anticonvulsant , morphine , (+) naloxone , pharmacology , clonidine , bicuculline , convulsion , antagonist , chemistry , agonist , convulsant , seizure threshold , endocrinology , medicine , epilepsy , receptor , psychiatry
Summary: Purpose: To evaluate the effect of the α 2 ‐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. Methods: 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. Results: 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). Conclusions: α 2 ‐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.