ALPHA-ADRENOCEPTOR AND OPIOID RECEPTOR MODULATION OF CLONIDINE-INDUCED ANTINOCICEPTION

1 The antinociceptive action of clonidine (Clon) and the interactions with alpha(1) alpha(2) adrenoceptor and opioid receptor antagonists wa s evaluated in mice by use of chemical algesiometric test (acetic acid writhing test). 2 Clon produced a dose-dependent antinociceptive acti on and the ED(50) for intracerebroventricular (i.c.v.) was lower than for intraperitoneal (i.p.) administration (1 ng kg(-1) vs 300 ng kg(-1 )). The parallelism of the dose-response curves indicates activation o f a common receptor subtype. 3 Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazo sin produced a dual action: i.c.v. Cion effect did not change, and i.p . Cion effect was enhanced. Yohimbine i.c.v. or i.p. did not induce an tinonciception, but antagonized Cion-induced activity. These results s uggest that alpha(1)- and alpha(2)-adrenoceptors, either located at th e pre- and/or postsynaptic level, are involved in the control of spina l antinociception. 4 Naloxone (NX) and naltrexone (NTX) induced antino ciceptive effects at low doses mu g kg(-1) range) and a lower antinoci ceptive effect at higher doses (mg kg(-1) range). Low doses of NX or N TX antagonized Cion antinociception, possibly in relation to a prefere ntial mu opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Cion, which could be due to an enhanced inhibition of the release of substance P. 5 The result s obtained in the present work suggest the involvement of alpha(1)-, a lpha(2)-adrenoceptor and opioid receptors in the modulation of the ant inociceptive activity of clonidine, which seems to be exerted either a t spinal and/or supraspinal level.