Meperidine effects on schedule-controlled responding.

The effect of meperidine were studied on responding by pigeons under a multiple fixed-ratio, fixed-interval schedule of food presentation. Low doses of meperidine (0.3-3 mg/kg) generally increased and higher doses decreased responding under the fixed-interval component of the multiple schedule. The responding under the fixed-ratio component was usually unaffected by low doses and decreased by doses greater than 3 mg/kg of meperidine. Naloxone (1 mg/kg) antagonized the rate increases in the fixed-interval component; however, no dose of naloxone (1-56 mg/kg) or cyclazocine (0.1-3 mg/kg) antagonized the rate decreases produced by meperidine under either schedule component. The effects of morphine and meperidine were compared in two birds treated daily with methadone. In a bird maintained on a daily dose of 120 mg/kg (p.o.) of methadone, there was a 10-fold shift of the dose-effect curve for morphine but no shift of the meperidine dose-effect curve. In a bird maintained on a daily dose of 30 mg/kg (p.o.) of methadone, there was a 3- to 5-fold shift of the morphine dose-effect curve, but again no shift of the meperidine dose-effect curve. Thus, the rate-decreasing effects of meperidine were not antagonized by narcotic antagonists, nor did they show cross-tolerance to methadone.