DISCRIMINATIVE STIMULUS EFFECTS OF OPIOIDS IN PIGEONS TRAINED TO DISCRIMINATE FENTANYL, BREMAZOCINE AND WATER - EVIDENCE OF PHARMACOLOGICALSELECTIVITY

The purpose of the present investigation was to examine the discrimina tive stimulus effects of opioids with activity at mu and kappa opioid receptors, in pigeons trained to discriminate the mu opioid fentanyl, the kappa opioid bremazocine and water in a three-choice discriminatio n task. The apparent pkB values obtained for naloxone as an antagonist of the stimulus effects of fentanyl were higher than those obtained a gainst the bremazocine stimulus. The mu opioids morphine and l-methado ne substituted for the fentanyl stimulus, the kappa opioids U50,488 an d U69,593 substituted for the bremazocine stimulus, and the non-opioid pentobarbital failed to substitute for either the fentanyl or bremazo cine stimulus. A series of opioids with activity at both the mu and ka ppa opioid receptor sites, including nalorphine, butorphanol, buprenor phine, nalbuphine, ethylketocyclazocine, (-)-ketocyclazocine, (-)-n-al lylnormetazocine (NANM) and levallorphan, produced high levels of subs titution for the fentanyl stimulus without producing appreciable level s of substitution for the bremazocine stimulus. At doses that did not substitute for the fentanyl stimulus, (-)-NANM, levallorphan, nalorphi ne and nalbuphine partially antagonized the bremazocine stimulus (i.e. produced responding on the water key). Butorphanol and buprenorphine also antagonized the bremazocine stimulus, although this effect was ev idenced only at doses that substituted for the fentanyl stimulus. In c ontrast, even when tested up to doses that markedly decreased rates of responding, ethylketocyclazocine and (-)-ketocyclazocine failed to an tagonize the bremazocine stimulus. The present findings indicate that in this three-choice task the fentanyl-like substitution patterns prod uced by opioids with activity at both the mu and kappa opioid receptor s are similar to those reported in pigeons trained to discriminate eit her fentanyl or bremazocine from saline (i.e. two-choice tasks). In th is task, however, the level of kappa antagonist activity evidenced by these opioids was considerably less than that obtained in pigeons trai ned to discriminate bremazocine from saline.