Previous experience of diazepam withdrawal prevents the formation of a withdrawal-conditioned taste aversion: test of a blocking hypothesis

Prior experience of withdrawal from chronic diazepam treatment reduces the aversiveness of withdrawal when precipitated withdrawal is made the unconditioned stimulus in a conditioned taste aversion (CTA) paradigm. Accounts of the mechanism hy which unconditioned stimulus pre-exposure reduces its effectiveness in CTA postulate that unconditioned stimulus pre-exposure leads to the formation of associations with the environment, resulting in blocking of taste conditioning. We tested whether a blocking explanation accounted for the reduced effectiveness of withdrawal as a unconditioned stimulus in a CTA following prior exposure. Mice received chronic diazepam (15 mg/kg/day, s.c in sesame oil), or sesame oil vehicle, for three periods of 7 days, interspersed with 3-day withdrawal periods. The first two withdrawals occurred either in the home cage, or in one compartment of a place-conditioning apparatus (PCA). Animals which experienced withdrawal in the home cage were given equivalent experience of the PCA outside the withdrawal period. The third withdrawal was precipitated by i.p. administration of flumazenil (20 mg/kg). Thirty minutes before injection, all animals were placed individually in the compartment of the PCA to which they had been previously exposed, allowed to drink a novel 10% sucrose solution, injected with flumazenil, and replaced in the PCA for 2 h, before being returned to the home cage. When sucrose consumption was measured 24 h later, only that group which had experienced all three withdrawals in the PCA showed evidence of a CTA. These animals (but not those that had experienced withdrawal in the home cage, or vehicle-treated mice) also shelved strong avoidance of the chamber in which they had experienced withdrawal. Thus, no evidence was adduced that prior conditioning of an environment-conditioned stimulus to a withdrawal unconditioned stimulus blocked the formation of a CTA. When the CTA conditioning was repeated in the home cage, again only the mice that had experienced withdrawal in the place-conditioning apparatus showed evidence of conditioning. These observations are discussed in the context of blocking explanations of unconditioned stimulus pre-exposure. (C) 2000 Lippincott Williams & Wilkins.