Delta opioid-like discriminative stimulus effects of mu opioids in pigeons discriminating the delta opioid BW373U86 from saline

The purpose of this experiment was to examine the substitution patterns produced by opioids with activity at the mu receptor in pigeons trained to discriminate the delta opioid BW373U86 from saline. A low dose of naltrindole (0.1 mg/kg) produced at least a 16-fold rightward shift in the dose-effect curve for the stimulus effects of BW373U86 (yielding a pK(B) = 7.9), whereas a relatively high dose of naloxone (1.0 mg/kg) produced only a 2-fold rightward shift (yielding a pK(B) = 5.6). The delta opioid SNC80 and the mixed mu/kappa opioids ethylketocyclazocine and ketocyclazocine substituted completely for the BW373U86 stimulus. Various opioids with activity at the mu receptor (levallorphan, [-]-cyclazocine, [-]-n-allylnormetazocine, morphine, butorphanol, nalbuphine, [+]-propoxyphene, etorphine, fentanyl) substituted partially for the BW373U86 stimulus. There was no relationship between the substitution patterns produced by these opioids and their relative intrinsic efficacy at the mu receptor, their relative selectivity for the mu receptor or their relative affinity for the delta receptor. Naloxone (1.0 mg/kg) was considerably more effective than naltrindole (0.1 mg/kg) in antagonizing the substitution patterns produced by etorphine, ethylketocyclazocine, ketocyclazocine and butorphanol, suggesting that these effects were not mediated by activity at the delta receptor. There was no evidence that these opioids antagonized the BW373U86 stimulus, suggesting that they were not functioning as low efficacy agonists at the delta receptor. The kappa opioids bremazocine and U50,488, as well as the non-opioids cocaine and pentobarbital, failed to produce appreciable levels of BW373U86 responding. The present findings indicate that in pigeons mu opioids most likely produce delta-like discriminative stimulus effects by activation of mu rather than delta or kappa receptors.