Tolerance to the discriminative stimulus effects of Δ9-tetrahydrocannabinol

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Abstract

Although tolerance to a variety of behavioral and physiological effects of Δ9 -tetrahydrocannabinol (Δ9-THC) has been demonstrated, previous studies have reported that tolerance to the discriminative stimulus effects of Δ9-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 Δ9-THC under conditions of supplemental administration during suspended training. Rats, trained to discriminate Δ9-THC (3 mg/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 Δ9-THC before and after repeated administration of vehicle and of high doses of Δ9-THC. Following suspended training with repeated vehicle injection, the Δ9-THC dose-effect curve for percentage of drug lever responding showed little change from the prevehicle curve. After supplemental administration of Δ9-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 Δ9-THC suggests that tolerance developed to the discriminative stimulus effects of Δ9-THC under suspended training conditions.

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