DISCRIMINATIVE STIMULUS EFFECTS OF BW373U86 - A NONPEPTIDE LIGAND WITH SELECTIVITY FOR DELTA-OPIOID RECEPTORS

Several opioid agonists were evaluated in pigeons trained to discrimin ate i.m. injections of sterile water from either the mu agonist morphi ne (5.6 mg/kg), the kappa agonist bremazocine (0.032mg/kg) or piperazi nyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86; 0.56 mg/kg). Pig eons were trained to peck one of two keys on a fixed-ratio 20 schedule for food reinforcement. The pattern of substitution of mu, kappa and delta selective agonists in the three groups of birds suggested that t he discriminative stimulus effects of morphine, bremazocine and BW373U 86 were different; however, a component of the discriminative stimulus effects of BW373U86 appeared to be shared with morphine. Apparent pA2 values for naltrexone with morphine, bremazocine and BW373U86 were 7. 6, 6.8 and 6.3, respectively. The apparent pA2 value for naltrindole w ith BW373U86 was 8.3. Naltrindole (1 0.0 mg/kg) produced a 3-fold shif t to the right in the dose-effect curve for morphine but did not antag onize bremazocine. Although results from the substitution experiments suggested that a component of the BW373U86 discriminative stimulus was mediated through mu opioid receptors, the fact that naltrindole was 1 000-fold more potent and naltrexone was 30-fold less potent in antagon izing BW373U86 than morphine indicated that the discriminative effects of BW373U86 were also mediated through delta opioid receptors.