Effect of Alpha-Adrenoceptor Agonists and Antagonists on Imipramine-Induced Antinociception in the Rat Formalin Test

Abstract

In this study, the effect of central administration of the α-adrenoceptor agents on the antinociception induced by imipramine in the formalin test has been investigated. Intraperitoneal (IP) administration of different doses of imipramine (10–80 mg/kg) and intracerebroventricular (ICV) administration of the α₂-adrenoceptor agonist clonidine (0.05–0.8 µg/rat) elicited a dose-dependent antinociception in the both phases of the test. Furthermore, different doses of clonidine (0.05–0.2 µg/rat) increased the antinociception induced by imipramine (10 and 20 mg/kg). The α₂-adrenoceptor antagonist yohimbine (2 µg/rat, ICV) reduced the response of a low dose imipramine (10 mg/kg, IP) plus different doses of clonidine (0.05, 0.1 and 0.2 µg/rat, ICV), but did not alter the response induced by higher doses of imipramine (20 and 40 mg/kg) alone or in combination with clonidine. Yohimbine by itself elicited no effect. The α₁-adrenoceptor agonist phenylephrine (0.07–1.5 µg/rat) induced antinociception in both phases of the formalin test, but did not alter the imipramine-induced antinociception. The α₁-adrenoceptor antagonist prazosin neither elicited antinociception nor altered the imipramine response. Yohimbine (2 µg/ rat, ICV) in combination with prazosin (0.5 µg/rat, ICV) caused more inhibition of the response of imipramine or imipramine plus clonidine. Therefore, it is concluded that α₂-adrenoceptor mechanism may be involved in the imipramine-induced antinociception.