Acute and chronic morphine administration: effects of mixed-action opioids in rats and squirrel monkeys responding under a schedule of food presentation.

The effects of several opioid compounds were examined in rats and squirrel monkeys responding under a fixed-ratio 30 schedule of food presentation. In rats, dose-effect curves were determined before and after acute pretreatment with 5.6 mg/kg of morphine 5 to 6 hr before the session, as well as during and after the termination of a chronic regimen in which rats received 30.0 mg/kg/day of morphine. In monkeys, dose-effect curves were determined before, during and after the termination of a chronic regimen in which monkeys received 6.0 mg/kg/day of morphine. In morphine-pretreated rats, dose-effect curves for the opioid antagonists naloxone, naltrexone and diprenorphine shifted to the left of those determined when rats were not morphine-pretreated; whereas those for the mu-opioid agonists morphine and I-methadone and mixed-action opioids nalorphine, nalbuphine, butorphanol, pentazocine and bremazocine were unaltered. During chronic morphine administration in rats, dose-effect curves for morphine and butorphanol shifted to the right; whereas the dose-effect curves for naloxone and nalorphine shifted to the left of those determined when rats were not treated with morphine. The effects of pentazocine, nalbuphine, bremazocine and the kappa-opioid agonist U50,488 were unaltered in morphine-maintained rats. In morphine-maintained monkeys, the dose-effect curves for morphine and I-methadone shifted to the right; whereas those for naloxone, nalorphine and nalbuphine shifted to the left of the prechronic dose-effect curves. Dose-effect curves for butorphanol, pentazocine and U50,488 were unaltered. Overall, these results suggest that the chronic morphine administration procedure can be used to distinguish opioid compounds based upon their relative mu agonist and antagonist activity.