Llfe Sciences PoSSible invOIVement Of u1~OpiOid receptOrS in the fentanyl- Or mOrphine-induced antinOCiceptiOn at

Fentanyl has been shown to be a potent analgesic with a lower propensity to produce tolerance and physical dependence in the clinical setting. The present study was designed to investigate the mechanisms of fentanyl- or morphine-induced antinociception at both supraspinal and spinal sites. In the mouse tail-flick test, the antinociceptive effects induced by both fentanyl and morphine were blocked by either the u I-opioid receptor antagonist naloxonazine or the u1/u2-0pioid receptor antagonist ~-funaltrexamine (~-FNA) afier s.c,, i,c.v. or i,t. injection. In contrast, both fentanyl and morphine given i,c.v. or i.t. failed to produce antinociception in u1-deficient CXBK mice. These findings indicate that like morphine, the antinociception induced by fentanyl may be mediated predominantly through rll-opioid receptors at both supraspinal and spinal sites in mice. We also determined the ED50 Values for s.c.-, i.c,v.- and i.t.-administered fentanyl- or morphine-induced antinociception in mice. The ED50 values for s,c.-, i,c.v.- and i.t.-administered fentanyl-induced antinociception were 73.7, 18,5 and 1.2-fold lower than that of morphine, respectively. The present data clearly suggest the usefulness of peripheral treatmen