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.
Zarrindast
Mohammed-Reza
MR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. zarinmr@ams.ac.ir
Sahebgharani
Mousa
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D007099:Imipramine / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000929:Antidepressive Agents, Tricyclic; D005557:Formaldehyde; D015016:Yohimbine; D003000:Clonidine; D007099:Imipramine; D011224:Prazosin