The role of central α-adrenergic receptors on imipramine-induced antinociception as revealed by formalin test in rat

In this study, the effect of α-adrenoceptor agents on imipramine-induced antinociception was investigated using formalin test. Intraperitoneal (i.p.) administration of imipramine at different doses (10-80 mg/kg) induced antinociception in both phases of formalin test. In addition, intracerebroventricular (i.c.v.) injection of imipramine (1, 5, and 10 µg/rat) did not elicit any effect, although i.c.v. injection of clonidine, an α2-adrenoceptor agonist at doses of 0.05-0.8 µg/rat also elicited antinociception in both phases of the test. Furthermore, clonidine increases the antinociception induced by imipramine and yohimbine, an α2-adrenoceptor antagonist at a dose of 2 µg/rat (i.c.v.) reduced the response to imipramine at a low dose (10 mg/kg, i.p.) and clonidine (0.05 µg/rat, i.c.v.), 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 response. Meanwhile, phenylephrine (0.07-1.5 µg/rat, i.c.v.), an αl-adrenoceptor agonist induced antinociception in both phases of formalin test, but did not alter the imipramine-induced antinociception. The αl -adrenoceptor antagonist, prazocin neither elicited antinociception nor altered the imipramine response. Yohimbine (2 µg/rat, i.c.v.) in combination with prazocin (0.5 µg/rat, i.c.v.) further inhibited the response for imipramine alone or in combination with clonidine. Taken together, it is concluded that α2-adrenoceptor-mediated mechanism might be involved in the development of imipramine-induced antinociception.