Discriminative stimulus effects of the nonpeptidic delta-opioid agonist SNC80 in rhesus monkeys

Five rhesus monkeys were trained to discriminate the nonpeptidic, delta-opi oid agonist SNC80 (0.32 mg/kg i.m.) from saline by using a food-reinforced drug-discrimination procedure. Cumulative doses of SNC80 produced a dose-de pendent increase in SNC80-appropriate responding and a dose-dependent decre ase in response rate. In time-course studies, peak effects of the training dose of SNC80 were observed after 15 min, and these effects diminished over 240 min. In substitution studies, other piperazinyl benzamide delta agonis ts (SNC86, SNC162, and SNC243A) substituted for SNC80 with relative potenci es similar those of SNC80. However, SNC67, the (-)-enantiomer of SNC80, did not occasion SNC80-appropriate responding up to a dose (32.0 mg/kg) that p roduced convulsions in one monkey. The mu agonists morphine and fentanyl an d the kappa agonists U-50,488 and enadoline failed to substitute for SNC80 up to doses that eliminated responding. Two nonopioids (the N-methyl-D-aspa rtate antagonist ketamine and the monoamine reuptake inhibitor cocaine) als o produced primarily saline-appropriate responding. Both the discriminative stimulus and rate-decreasing effects of SNC80 were antagonized by the delt a-selective antagonist naltrindole (0.01-1.0 mg/kg) but not by doses of the opioid antagonist quadazocine (0.1-1.0 mg/kg) that block the effects of mu and kappa agonists. These data suggest that the discriminative stimulus ef fects of SNC80 are mediated by delta-opioid receptors and that the discrimi native stimulus effects of delta opioids in primates can be differentiated from the effects of other opioid and nonopioid compounds.