Effect of α-adrenoceptor agents on imipramine-induced antinociception in nerve-ligated mice

In this study, the effects of adrenoceptor agonists and antagonists on antinociception induced by imipramine in sciatic-nerve-ligated mice were investigated. The response of different doses of morphine, imipramine and adrenoceptor agonists and antagonists was examined 14 days after unilateral nerve-ligation in the hot-plate test. Intraperitoneal injection of different doses of morphine (3. 6 and 9 mg/kg), imipramine (10, 20 and 30 mg/kg), the alpha (2)-adrenoceptor agonist, clonidine (0.05, 0.1 and 0.2 mg/kg) or the alpha (1)-adrenoceptor agonist, phenylephrine (3, 4 and 8 mg/kg) induced dose-related antinociception in both intact and nerve-ligated mice. The antinociception induced by morphine but not that of imipramine, clonidine or phenylephrine, in nerve-ligated mice was significantly less than that induced in intact animals. Imipramine in combination with clonidine tends to induce a higher response, but the combination of imipramine with phenylephrine did nor lead to significant potentiation. The alpha (2)-adrenoceptor antagonist, yohimbine, reduced the response induced by imipramine or imipramine plus clonidine in intact and nerve-ligated animals. However, the alpha (1)-adrenoceptor antagonist, prazosin, did not alter imipramine response. It may be concluded that imipramine induced antinociception in both intact and nerve-ligated mice through an alpha (2)-adrenoceptor mechanism(s). (C) 2001 Elsevier Science B.V. All lights reserved.