Effects of picenadol and its agonist and antagonist isomers on schedule-controlled behavior

The effects of picenadol and its (+)- and (-)-isomers were determined on the responding of pigeons under a multiple fixed-ratio (FR) 50-response, fixed-interval (FI) 5-min schedule of grain presentation. Picenadol decreased responding in both schedule components as a function of dose (0.64-10 mg/kg). Naloxone shifted to the right the picenadol dose-effect curve in the FR component (2.8-fold), but had little effect on the dose-effect curve for FI responding. Similarly, the (+)-isomer decreased responding in both schedule components, but naloxone was only able to shift to the right the dose-effect curve for the (+)-isomer on FR responding (2-fold). The effects of the (+)-isomer on FI responding were not affected by naloxone. The (-)-isomer decreased responding at high doses (20 and 40 mg/kg) and this effect was not antagonized by naloxone. The dose-effect curves for the (-)-isomer were shifted markedly to the left in animals maintained on daily doses (30 or 60 mg/kg p.o.) of methadone. Low doses (2.5-20 mg/kg) of the (-)-isomer antagonized the behavioral suppressant effects of 5 mg/kg of l-methadone. The (+)-isomer, but not the (-)-isomer, antagonized the complete behavioral suppression produced by 0.05 mg/kg of oxotremorine.(ABSTRACT TRUNCATED AT 250 WORDS)