Supraspinal antinociception produced by [D-Met 2]-FMRFamide in mice

Abstract

The ability of Phe-Met-Arg-Phe-NH 2 (FMRFamide) or [D-Met 2]-FMRFamide to produce antinociception in mice, or to block morphine-induced antinociception, was examined using the tail-flick and tail-immersion (55°C) tests. [D-Met 2]-FMRFamide dose-dependently produced antinociception following intracerebroventricular (i.c.v.) administration with ED 50 values (95% confidence limits) of 5.0 (2.2–7.2) and 12.8 (8.1–19.9) μg in the tail-flick and tail-immersion tests, respectively. FMRFamide did not produce a maximal effect in the tail-flick test. Naloxone (administered s.c. 20 min prior to the i.c.v. administration of [D-Met 2]-FMRFamide) dose-dependently attenuated [D-Met 2]-FMRFamide-induced antinociception. The shift in the [D-Met 2]-FMRFamide dose-response curve was parallel and a pA 2 value for naloxone of 6.3 ± 0.3 was determined from a Schild plot analysis. Mice made tolerant to the antinociceptive effect of morphine were cross-tolerant to the antinociceptive effect of [D-Met 2]-FMRFamide. FMRFamide and [D-Met 2]-FMRFamide both produced rightward, parallel shifts of the morphine antinociceptive dose-response curve. The findings that [D-Met 2]-FMRFamide both elicited naloxone-sensitive antinociception and attenuated morphine-induced antinociception are consistent with the view that FMRFamide-related peptides (FaRPs) are weak agonists at opioid receptors and, further, appear to reconcile the apparently chimeric agonist and antagonist properties of these peptides observed in vivo.