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

Abstract

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 naltre