Discriminative stimulus and antinociceptive effects of dihydroetorphine in rhesus monkeys

Rationale: Although dihydroetorphine has μ opioid agonist activity there is evidence to suggest that it is not identical to that of morphine. Objective: This study compared dihydroetorphine to other opioids under behavioral conditions that are sensitive to μ opioid agonism. Methods: The acute effects of dihydroetorphine, etorphine and morphine were evaluated using two procedures. In one procedure, monkeys received 3.2 mg/kg per day of morphine and discriminated naltrexone from saline while responding under a fixed-ratio 5 schedule of stimulus shock termination. In addition, a warm-water, tail-withdrawal procedure was used in untreated monkeys. Results: When acutely deprived of morphine, monkeys responded on the naltrexone lever, and this effect was reversed by dihydroetorphine, etorphine and morphine. Each agonist produced the maximum (20-s latency) antinociceptive effect in 50°C water. Naltrexone antagonized the discriminative stimulus and antinociceptive effects of dihydroetorphine and etorphine, although Schild analyses yielded large variability in slopes and pA₂ values. Naltrexone reversed established effects of dihydroetorphine and morphine in both procedures and pretreatment with dihydroetorphine (2, 6 or 24 h) did not alter the discriminative stimulus effects of morphine. Conclusions: Taken together, these data support the notion that dihydroetorphine is a μ agonist with a short duration of action; however, variability in antagonism of dihydroetorphine and morphine might be a manifestation of differences that have been reported for these drugs at the cellular level.