Schedule-dependent tolerance to behavioral effects of delta 9-tetrahydrocannabinol when reinforcement frequencies are matched.

Squirrel monkeys pressed a lever under a multiple interresponse-time greater than 28-sec, modified random-interval schedule which provided comparable frequencies and temporal distributions of food pellet presentation in the two components. Daily intramuscular administration of either 0.25 or 1.00 mg/kg delta 9-tetrahydrocannabinol resulted initially in suppression and/or disruption of responding and concomitant decreases in the frequency of food presentation in both components. Responding in both components next increased, resulting in recovery of baseline frequencies of pellet delivery during the random-interval component, but continued depression during the interresponse-time schedule. The drug-induced changes in responding under the interresponse-time schedule diminished with repeated injections, whereas response rates during the random-interval schedule sometimes remained elevated. Interresponse-time distributions under the interresponse-time schedule showed that with repeated administration of the drug only those characteristics which had the greatest effect on reinforcement frequency recovered to baseline levels. When drug injections were replaced by daily injections of the vehicle, responding was greatly disrupted only during the random-interval component. These findings are only partially consistent with other results which suggest aht tolerance development to the behavioral effects of delta 9-tetrahydrocannabinol is greatly enhanced if the drug initially produces reinforcement loss.