Ketamine: acquisition and retention of classically conditioned responses during treatment with large doses.

Two experiments were conducted in rabbits to examine the effects of ketamine (0, 100, and 200 mg/kg) on the acquisition and retention of the classically conditioned nictitating membrane response (NMR). Classical conditioning of the NMR was accomplished by pairing tone and light conditioned stimuli (CS) with paraorbital shock as the unconditioned stimulus (UCS). Experiment 1 assessed the effects of the drug on acquisition and retention of conditioned responses (CR) and determined the role of previous exposure to the experimental environment. Ketamine blocked the display of CR. However, data from subsequent retention testing under nondrug conditions revealed that rabbits that had previously received 100 mg/kg ketamine learned faster than saline-treated rabbits during the acquisition phases. Rabbits that received 100 mg/kg ketamine and were placed in the experimental chambers, but not presented with stimuli during the acquisition phase, did not learn faster during the retention phase than naive rabbits. Experiment 2 controlled further for the effects of nonassociative, unlearned processes. Control groups were presented with unpaired CS and UCS training after drug administration, and subsequently received conventional acquisition sessions under nondrug conditions. Their data indicated that the ketamine group's rapid acquisition during retention testing could not be attributed to nonassociative factors. We conclude that, although it was impossible directly to observe acquisition in rabbits under the influence of ketamine, it was possible that learning occurred as manifested by "savings" in subsequent learning trials.