Methadone-induced attenuation of the effects of delta 9-tetrahydrocannabinol on temporal discrimination in pigeons.

Pigeons responded under a discrete trial procedure in which they were required to peck one of two keys depending on the duration of a conditional stimulus (general illumination of the experimental chamber). Correct choices (red key after a 4-sec stimulus; green key after an 8-sec stimulus) resulted in the intermittent presentation of food; incorrect choices resulted in a darkened chamber. Intermediate durations (probe stimuli) were also presented occasionally. The effects of tetrahydrocannabinol (THC; 0.06-0.50 mg/kg) and repeated methadone injections (2-20 mg/kg/day) were assessed alone and in combination. THC resulted in a dose-dependent decrease in accuracy with the greater effect on long-duration trials. Repeated methadone alone resulted in a decrease in accuracy only when the methadone dose was changed. High doses of methadone (6 and 20 mg/kg/day) resulted in either a complete (0.25 mg/kg of THC) or partial (0.50 mg/kg of THC) attenuation of effects of THC on temporal discrimination accuracy as compared to a low methadone dose (2 mg/kg/day) or THC alone. The results suggest the possibility of cross-tolerance or antagonism between methadone and THC.