EFFECTS OF DRUGS ON BEHAVIOR IN PIGEONS TOLERANT TO DELTA-9-TETRAHYDROCANNABINOL

Abstract

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 a 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 dose of .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 3 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 3 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 form .DELTA.9-THC to pentobarbital.