Morphine, saline and naltrexone discrimination in morphine-treated pigeons

Pigeons responding under a fixed-ratio 20 schedule of food presentation were treated with 10.0 mg/kg/day of morphine and trained to discriminate among i.m. injections of 17.8 mg/kg of morphine, saline and 0.032 mg/kg of naltrexone. Morphine and naltrexone occasioned responding on the injection-appropriate keys at doses greater than or equal to 32.0 and 0.032 mg/kg, respectively. Termination of morphine injections also produced naltrexone-appropriate responding, suggesting that the withdrawal-precipitating actions of naltrexone account for its discriminative stimulus effects in morphine-treated pigeons. The potency of morphine as a discriminative stimulus was similar in 30-hr morphine-abstinent pigeons and in pigeons that had received morphine 6 hr before testing. The opioid antagonists naloxone, nalmefene and diprenorphine substituted as discriminative stimuli for naltrexone at doses greater than or equal to 0.032 mg/kg. Nalorphine, a mixed agonist-antagonist, also substituted for naltrexone, but only at doses larger than 10.0 mg/kg. The mixed agonist-antagonist pentazocine failed to substitute for either training drug; the opioid agonist levorphanol substituted completely for morphine. Naltrexone was 1000 times more potent as a discriminative stimulus and 17.5 times more potent in suppressing responding in morphine-treated compared with untreated pigeons. In contrast, the acute dose of naltrexone required to prevent the discriminative stimulus effects of morphine was not changed by daily morphine injections. Acute injections of morphine attenuated the discriminative stimulus effects of naltrexone. Mutual antagonism between morphine and naltrexone suggests that these drugs exert discriminative stimulus effects by opposing actions at the same receptors.