Tolerance to the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol

Although tolerance to a variety of behavioral and physiological effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) has been demonstrated, previous studies have reported that tolerance to the discriminative stimulus effects of Delta(9)-THC does not develop when discrimination training is continued during repeated administration. The present study investigated development of tolerance to the discriminative stimulus effects of Delta(9)-THC under conditions of supplemental administration during suspended training. Rats, trained to discriminate Delta(9)-THC (3mg/kg) from vehicle in a two-lever drug discrimination procedure, under a fixed-ratio 10 schedule of food reinforcement, were tested with cumulative doses of Delta(9)-THC before and after repeated administration of vehicle and of high doses of Delta(9)-THC. Following suspended training with repeated vehicle injection, the Delta(9)-THC dose-effect curve for percentage of drug lever responding showed little change from the prevehicle curve. After supplemental administration of Delta(9)-THC, the degree of rightward shift in the post-THC dose-effect curve was 40-fold. Recovery to pre-THC levels of percentage of drug lever responding was observed during a second post-THC dose-effect curve administered 23 days later. The large reversible shift in the dose-effect curve following supplemental administration of Delta(9)-THC suggests that tolerance developed to the discriminative stimulus effects of Delta(9)-THC under suspended training conditions.