Effect of Î±2 adrenergic agents upon central etorphine antinociception in the cat
Systemic (s.c.) administration of Î±2 agonists clonidine (25-100 Î¼g/kg) or guanfacine (50-400 Î¼g/kg) elicited antinociception as assessed by the cat tail-flick model and potentiated in a dose-dependent manner the antinociceptive effect of etorphine (2.5 Î¼g) administered directly into the periaqueductal gray. Conversely, systemic yohimbine (1 mg/kg) attenuated the effects of central etorphine, and diminished potentiation of etorphine by the Î±2 agonists. Prior microinjection of clonidine (5Î¼g) or guanfacine (5 Î¼g) into the locus coeruleus (LC) reduced the intensity of central etorphine antinociception whereas central yohimbine (20 Î¼g) pretreatment increased peak antinociceptive activity and prolonged the duration of etorphine. Thus, systemic Î±2 agonists are inherently antinociceptive and potentiate central narcotic antinociception; however, the site of interaction between Î±2 agonists and opiates does not appear to be the LC inasmuch as Î±2 agonists attenuate the antinociceptive effect of etorphine when administered directly into the LC. A spinal site of action is suggested based upon known LC-spinal projections and our experimental observations. Â© 1984.
Ossipov, M. H.; Malseed, R. T.; Eisenman, L. M.; and Goldstein, Frederick J., "Effect of Î±2 adrenergic agents upon central etorphine antinociception in the cat" (1984). PCOM Scholarly Papers. 1336.