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  • Title: Tolerance to the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol.
    Author: Wiley JL, Barrett RL, Balster RL, Martin BR.
    Journal: Behav Pharmacol; 1993 Dec; 4(6):581-585. PubMed ID: 11224227.
    Abstract:
    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.
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