Discriminative stimulus properties of naloxone

Nonopioid-dependent pigeons were trained to discriminate IM injections of 30.0 mg/kg naloxone from water in the procedure in which 15 consecutive responses on one of two keys resulted in grain presentation. Naloxone-appropriate responding was maximal at doses of naloxone equal to and greater than the training dose. The onset of the naloxone discriminative cue was rapid (less than 5 min) and the duration of the cue was short (less than 60 min). Naltrexone (1.0-10.0 mg/kg). pentazocine (1.0-10.0 mg/kg), levallorphan (1.0-30.0 mg/kg), and nalorphine (3.0-30.0 mg/kg) produced dose-dependent increases in naloxone-appropriate responding, occasioning 100% naloxone-key selections. In contrast, cyclazocine, profadol, and diprenorphine, at doses up to those at which animals did not respond, produced only intermediate degrees of naloxone-appropriate responding. Morphine always produced selection of the water key. These results demonstrate that a pure opioid antagonist, such as naloxone, has discriminative stimulus effects in the nonopioid-dependent animals, that these stimulus effects are shared by certain other opioid antagonists, and that these effects are distinguishable from those produced by pure opioid agonists, such as morphine.