EVALUATION OF THE DISCRIMINATIVE STIMULUS AND REINFORCING EFFECTS OF DIHYDROETORPHINE

These experiments examined whether dihydroetorphine (DHE) could serve as a reinforcer in rhesus monkeys and evoke the discriminative stimulu s effects of heroin (HER) in rats, two procedures useful in predicting the overall abuse potential of compounds. Rhesus monkeys were trained to self-administer i.v. HER (10 mu g/kg for monkeys M-BA, M-NI, and M -HO; 3 mu g/kg for monkey M-PO) during daily, 2-h experimental session s under FR 10 Timeout 4 min schedules. VEH and doses of HER (1-30 mu g /kg), codeine (COD; 30-1000 mu g/kg), and DHE (1-100 ng/kg) were then substituted for the HER maintenance doses. Results indicated that DHE served as a reinforcer. The dose of DHE that maintained peak numbers o f infusions was 171 and 8571 times smaller than those maintaining peak numbers of infusions of heroin and codeine, respectively. Additionall y, male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg HER s.c. from vehicle (VEH) in an FR 10 (fixed-ratio 10), food-reinforced , operant procedure. During tests, HER, morphine (MOR), and DHE dose-d ependently evoked heroin-lever responding with ED(50)s of 0.055, 0.74, and 0.00033 mg/kg, respectively. These results indicate that DHE is s elf-administered by rhesus monkeys, and potently produces the discrimi native stimulus effects of HER in rats, and suggest that DHE would hav e a substantial potential for abuse. (C) 1997 Elsevier Science Ireland Ltd.