Effects of narcotic agonists and antagonists on schedule-induced water and morphine ingestion

A pattern of lever pressing and schedule-induced polydipsia was maintained in rats by a fixed-interval 90-second of food presentation. The effects of acute morphine, methadone, nalorphine, naloxone, pentazocine and cyclazocine were studied in control rats (morphine-free rats) and rats maintained on 200 mg/kg daily oral infections of morphine (morphine-maintained rats). The effects of morphine, nalorphine and naloxone also were studied in rats that were drinking a 0.5 mg/ml of morphine solution (morphine-drinking rats) in the experimental apparatus. All six drugs decreased drinking in the morphine-free rats. Pentazocine and naloxone increased lever-pressing rates in the morphine-free rats, while morphine, methadone, nalorphine and cyclazocine only decreased lever-pressing rates. In the morphine-maintained rats, the dose-effect curves for both lever-pressing and drinking measures were shifted to the left for naloxone, nalorphine, pentazocine and cyclazocine, indicating an increased sensitivity to the antagonists, while the dose-effect curves for morphine and methadone were shifted to the right, indicating that the morphine-maintenance regimen had produced tolerance to these drugs. Morphine and methadone injections increased drinking in the morphone-maintained rats, but none of the drugs increased lever-pressing rates in the morphine-maintained rats. In the morphine-drinking rats, morphine decreased lever pressing at doses that left licking rates unaffected. Since the effects of morphine in the morphine-drinking rats differed from those in the morphine-free rats or the morphine-maintained rats, the effects of morphine on the self-ingestion of morphine in the experimental setting cannot be attributed entirely to the schedule of pellet delivery or to the effect of chronic morphine dosing.