Effects of drugs on behavior in pigeons tolerant to delta 9-tetrahydrocannabinol.

Schedule-controlled behavior was used to study how drug effects on behavior are modified by the development of tolerance to delta 9-tetrahydrocannabinol (delta 9-THC). Dose-effect curves were determined for pentobarbital, d-amphetamine and morphine on responding maintained by a multiple fixed-ratio fixed-interval schedule of food presentation in pigeons. The dose-effect curves were redetermined in combination with single injections of 1.0 mg/kg dose of delta 9-THC (which itself did not affect rates of responding) in birds made tolerant to delta 9-THC by multiple injections, and in combination with the 1.0 mg/kg delta 9-THC in birds tolerant to delta 9-THC. Acute doses of 1.0 mg/kg delta 9-THC potentiated the rate-decreasing effects of all three drugs. Pigeons tolerant to delta 9-THC were cross-tolerant to pentobarbital but not to d-amphetamine and morphine. Tolerance to delta 9-THC attenuated the potentiation of the effects of all three drugs by delta 9-THC. Determination of plasma pentobarbital levels in pigeons tolerant to delta 9-THC suggested that a drug dispositional mechanism played a role in the cross-tolerance from delta 9-THC to pentobarbital.