This proposal seeks to determine regional cerebral blood flow (CBF) changes associated with anticipation of infusion of ketamine. It is the first of a series of planned studies in delineating CBF changes in anticipation of a variety of psychotrophic probes. It is necessary to separate anticipation of placebo responses to fully interpret CBF changes to active psychopharmacologic agents and their mechanisms of action. We will study 30 normal controls after infusion of placebo and measure CBF using six H215O infusions and positron emission tomography (PET). Three groups of ten subjects will have different pre-exposure to ketamine: 1) prior infusion of active ketamine (0.3 m/kg) in double blind placebo controlled design; 2) a description of ketamine effects; and 3) no ketamine information. Groups 1 and 2 will be instructed they will receive ketamine or placebo during the PET scanning. Group 3 will be instructed that they will receive placebo. We hypothesize a graduated increase in anterior cingulate cortex in the three groups with the first group showing the most and third the least change due to anticipation of active drug.
