BEHAVIORAL-EFFECTS OF THE DELTA-SELECTIVE OPIOID AGONIST SNC80 AND RELATED-COMPOUNDS IN RHESUS-MONKEYS

The behavioral effects of the nonpeptidic delta opioid agonist SNC80 a nd a series of related piperazinyl benzamides derived from the parent compound BW373U86 were evaluated in rhesus monkeys. SNC80 (0.1-10 mg/k g) decreased response rates maintained by food-reinforcement in a dose - and time-dependent manner, with maximal effects occuring within 10 m in of intramuscular injection. The potency of SNC80 and five other pip erazinyl benzamides in this assay of schedule-controlled responding co rrelated with their affinity at cloned human delta opioid receptors bu t not with their affinity for cloned human mu receptors. Moreover, the effects of SNC80 were selectively antagonized by the delta-selective antagonist naltrindole (1.0 mg/kg), but not by the mu selective antago nist quadazocine (0.1 mg/kg) or the kappa-selective antagonist norbina ltorphimine (3.2 mg/kg). These findings indicate that SNC80 functions as a systemically active, delta-selective agonist with a rapid onset o f action in rhesus monkeys. The antinociceptive effects of SNC80 were examined in a warm-water tail-withdrawal assay of thermal nociception. SNC80 (0.1-10 mg/kg) produced weak but replicable antinociceptive eff ects that were antagonized by naltrindole (1.0 mg/kg). SNC80 antinocic eption was also dose-dependently antagonized by BW373U86 (0.56-1.0 mg/ kg), which was inactive in this procedure. These findings suggest that SNC80 may have higher efficacy than BW373U86 at delta opioid receptor s. Moreover, SNC80 at doses up to 32 mg/kg did not produce convulsions , which suggests that SNC80 may also be safer than BW373U86. The effec ts of SNC80 were also examined in monkeys trained to discriminate coca ine (0.4 mg/kg i.m.) or self-administer cocaine (0.032 mg/kg/injection ,i.v.). In drug discrimination studies, SNC80 (0.1-10 mg/kg) produced a dose-dependent and naltrindole-reversible increase in cocaine-approp riate responding, and complete substitution for cocaine was observed i n five of seven monkeys tested. However, SNC80 (1.0-100 mu g/kg/inject ion) did not maintain responding in monkeys trained to self-administer cocaine. Thus, despite its ability to produce cocaine-like discrimina tive stimulus effects, SNC80 may have relatively low abuse potential.