Augmentation of the development of behavioral tolerance to cannabinoid administration through pavlovian conditioning

This investigation examined the effects, in female rats, of a Pavlovian conditioning paradigm on the development of tolerance to hypolocomotion induced by the cannabinoid agonist HU-210. Rats were administered HU-210 and placebo in either an associative or a nonassociative fashion. The results indicated that rats in the associative paradigm developed tolerance significantly faster than those in the nonassociative group (p < 0.03). Subsequently, once tolerance had developed, the associative group of rats was administered HU-210 and placebo in the opposite environments. There were no differences found in locomotion between the CS+ and CS- environments following administration of HU-210. However, when the placebo was administered in the CS+ environment, there was a trend towards increased activity levels (p = 0.06), suggesting withdrawal-like behavior. These findings indicate that the underlying physiological mechanisms of tolerance development in the cannabinoid system are hastened by conditioning, but that these physiological alterations are not contingent upon the associative parameters used for drug administration.