A growing body of evidence suggests that deficits in glutamatergic function may underlie the pathophysiology of schizophrenia. Phencyclidine (PCP) is a noncompetitive antagonist for the NMDA-type glutamate receptor. Ketamine is an FDA approved anesthetic agent. It has an initial half-life of 15 minutes and a terminal half-life of 2 hours. General anesthetic doses of ketamine range from 1mg/kg to 3mg/kg IV bolus, with subsequent administration used as needed to maintain anesthesia Ketamine is a noncompetitive NMDA receptor antagonist and has been used in subanesthetic doses to probe glutamatergic function in healthy subjects, schizophrenic patients and chronic pain patients. In the present study, we proposed to examine the effects of Ketamine on behavioral, neuroendocrine and neuro-psychological parameters in neuroleptic-free schizophrenic patients and matched controls using a double-blind, counter-balanced placebo controlled design. To explore the effects of antipsychotic treatment on glutamatergic function, Ketamine will be given to schizophrenic patients while they are being treated with neuroleptic medications. In addition, the effects of Ketamine on metabolic rate and blood flow will be examined. The present study will be amended to a previously approved PET protocol (#93-M-01121) for the PET/Ketamine study.
