Effect of alpha-adrenoceptor agonists and antagonists on imipramine-induced antinociception in the rat formalin test

In this study, the effect of central administration of the alpha-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 alpha(2)-adrenoceptor agonist clonidine (0.05-0.8 microg/rat) elicited a dose-dependent antinociception in the both phases of the test. Furthermore, different doses of clonidine (0.05-0.2 microg/rat) increased the antinociception induced by imipramine (10 and 20 mg/kg). The alpha(2)-adrenoceptor antagonist yohimbine (2 microg/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 microg/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 alpha(1)-adrenoceptor agonist phenylephrine (0.07-1.5 microg/rat) induced antinociception in both phases of the formalin test, but did not alter the imipramine-induced antinociception. The alpha(1)-adrenoceptor antagonist prazosin neither elicited antinociception nor altered the imipramine response. Yohimbine (2 microg/ rat, ICV) in combination with prazosin (0.5 microg/rat, ICV) caused more inhibition of the response of imipramine or imipramine plus clonidine. Therefore, it is concluded that alpha(2)-adrenoceptor mechanism may be involved in the imipramine-induced antinociception.