Antinociceptive effects of [D-Ala2]deltorphin II, a highly selective [delta] agonist in vivo

Abstract

The present study has characterized the antinociceptive actions of [D-Ala2]deltorphin II following intracerebroventricular (i.c.v.) administration in the mouse tail-flick test. [D-Ala2]deltorphin II produced dose- and time-related antinociception, with maximal effects at +10 min and significant antinociception which lasted for 40-60 min. [D-Ala2]deltorphin II was 13-fold more potent than i.c.v. [D-Pen2, D-Pen5]enkephalin (DPDPE), a second highly selective [delta] agonist, and approximately equipotent with i.c.v. morphine in producing antinociception. The antinociceptive effects of i.c.v. [D-Ala2]deltorphin II and DPDPE, but not those of morphine, were antagonized by the selective [delta] antagonist, ICI 174,864. In contrast, pretreatment with the non-equilibrium [mu] antagonist, [beta]-funaltrexamine blocked morphine antinociception, but failed to antagonize [D-Ala2]deltorphin II and DPDPE antinociception. These data indicate that [D-Ala2]deltorphin II produced its antinociceptive effects at a supraspinal [delta] receptor. [D-Ala2]deltorphin II appears to be the most appropriate [delta] opioid agonist currently available for studies in vivo and support the involvement of [delta] receptors in supraspinal antinociception.