SEX-DIFFERENCES IN THE ANTINOCICEPTIVE EFFECTS OF THE ENKEPHALINASE INHIBITOR, SCH-34826

The effects of endogenous opioid peptides are limited by proteolytic e nzymes such as endopeptidase 24.11 (''enkephalinase''), which cleaves the Gly-Phe bonds in Met- and Leu-enkephalin. SCH 34826 arbonyl]-2-phe nylethyl]-L-phenylalanine-B-alamine) is a potent, highly specific, enk ephalinase inhibitor that has marked analgesic effects in laboratory r odents. The present study compared the effects of SCH 34826 on nocicep tion and restraint stress-induced opioid analgesia in reproductive adu lt male and female deer mice, Peromyscus maniculatus. SCH 34826 had si gnificantly greater antinociceptive actions and facilitatory effects o n stress-induced analgesia in male than female mice. These antinocicep tive effects of SCH 34826 were reduced by the general opioid antagonis t naloxone and completely blocked by the specific delta opioid recepto r antagonist, ICI 174,864, and nonsignificantly affected by the mu and kappa opioid receptor antagonists, beta-funaltrexamine and nor-binalt orphimine, respectively. These results show that there are s'' differe nces in the effects of the enkephalinase inhibitor, SCH 34826, on opio id-mediated antinociception and that these sex differences are associa ted with delta opioid mechanisms.