Discriminative stimulus and antinociceptive effects of dihydroetorphine in rhesus monkeys

Abstract

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.