Effect of a subanesthetic dose of ketamine on memory and conscious awareness in healthy volunteers

Rationale: Ketamine is an NMDA receptor antagonist with psychotogenic and c ognitive effects in healthy volunteers and schizophrenic patients which has been proposed to be a useful tool to investigate neurobiological basis of schizophrenia. Objective.The present study characterized the effects of a s ubanesthetic dose of ketamine on memory and related subjective states of aw areness in healthy volunteers. Methods: Twenty-six subjects were given eith er a 60-min ketamine (0.5 mg/kg per hour) or a placebo infusion. To obtain constant plasma ketamine throughout the experiment, ketamine was administer ed using a computer-controlled infusion system. Subjects carried out episod ic memory tasks involving words presented before and during infusion. Memor y performance was assessed with recognition and free recall tasks. Subjecti ve states of awareness were assessed using an experiential approach. Levels of psychopathology were evaluated with BPRS. Results: Ketamine impaired pe rformance in free recall and recognition of words presented during, but not before, infusion. There were no differences between groups concerning stat es of awareness associated with recognition memory. Subjects under ketamine had higher BPRS total scores as well as BPRS negative and positive cluster scores than con trol subjects. Conclusions: Ketamine decreases episodic me mory performance by impairing encoding, but not retrieval processes. It doe s not selectively impair subjective states of awareness associated with rec ognition memory as it has been seen in patients with schizophrenia. Ketamin e might mimic the memory impairment associated with acute, but not chronic, forms of schizophrenia.