Discriminative stimulus effects of BW373U86: a nonpeptide ligand with selectivity for delta opioid receptors.

Several opioid agonists were evaluated in pigeons trained to discriminate i.m. injections of sterile water from either the mu agonist morphine (5.6 mg/kg), the kappa agonist bremazocine (0.032mg/kg) or (+/-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1- piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86; 0.56 mg/kg). Pigeons were trained to peak 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 the discriminative stimulus effects of morphine, bremazocine and BW373U86 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 with BW373U86 was 8.3. Naltrindole (10.0 mg/kg) produced a 3-fold shift to the right in the dose-effect curve for morphine but did not antagonize bremazocine. Although results from the substitutions experiments suggested that a component of the BW373U86 discriminative stimulus was mediated through mu opioid receptors, the fact that naltrindole was 1000-fold more potent and naltrexone was 30-fold less potent in antagonizing BW373U86 than morphine indicated that the discriminative effects of BW373U86 were also mediated through delta opioid receptors.