α-Adrenoceptor and opioid receptor modulation of clonidine-induced antinociception

1. The antinociceptive action of clonidine (Clon) and the interactions with α₁, α₂ adrenoceptor and opioid receptor antagonists was evaluated in mice by use of chemical algesiometric test (acetic acid writhing test). 2. Clon produced a dose-dependent antinociceptive action and the ED₅₀ 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 of a common receptor subtype. 3. Systemic administration of prazosin and terazosin displayed antinociceptive activity. Pretreatment with prazosin produced a dual action: i.c.v. Clon effect did not change, and i.p. Clon effect was enhanced. Yohimbine i.c.v. or i.p. did not induce antinonciception, but antagonized Clon-induced activity. These results suggest that α₁- and α₂-adrenoceptors, either located at the pre- and/or postsynaptic level, are involved in the control of spinal antinociception. 4. Naloxone (NX) and naltrexone (NTX) induced antinociceptive effects at low doses (μg kg^-1 range) and a lower antinociceptive effect at higher doses (mg kg^-1 range). Low doses of NX or NTX antagonized Clon antinociception, possibly in relation to a preferential μ opioid receptor antagonism. In contrast, high doses of NX or NTX increased the antinociceptive activity of Clon, which could be due to an enhanced inhibition of the release of substance P. 5. The results obtained in the present work suggest the involvement of α₁-, α₂-adrenoceptor and opioid receptors in the modulation of the antinociceptive activity of clonidine, which seems to be exerted either at spinal and/or supraspinal level.