PET Whole Body Distribution Studies Using [11C]CUMI

Background: * Researchers studying new treatments for major depressive disorder are looking at how medications to treat depression act on the brain chemical serotonin, which interacts with specific serotonin receptors on brain cells. New methods of studying serotonin receptors in the brain may help provide a better understanding of depression and treatment options. * A new radioactive chemical called \[11C\]CUMI may be useful for studying serotonin receptors in the brain. By using positron emission tomography (PET) scanning to see how \[11C\]CUMI bonds with serotonin receptors, researchers will investigate whether \[11C\]CUMI can be used to study depression and how antidepressant medications work. Objectives: \- To determine the usefulness of \[11C\]CUMI as a method of studying serotonin receptors in the brain. Eligibility: \- Healthy individuals between 18 and 65 who have no history of psychiatric illness. Design: * This study requires 8 outpatient visits to the NIH clinic. * Visit 1: Participants will have a full physical examination and medical history, as well as a psychiatric evaluation and questions about alcohol and drug use. Other tests will include blood and urine samples and an electrocardiogram (EKG). Testing will take approximately 3 hours. * Visit 2: Participants will have a magnetic resonance imaging (MRI) scan to evaluate brain function and activity. * Visit 3: Participants will have a PET scan, in which a small amount of the radioactive chemical \[11C\]CUMI will be injected through an intravenous (IV) catheter, and will have another IV line put in place to draw regular blood samples during the scan. The scan will last approximately 4 hours. * Visits 4-8: Participants will have regular blood tests after the scan between days 1-3 and at about weeks 1, 2, 3, and 4. The blood tests will check muscle, heart, and liver function.

Eighteen million people in the United States are currently suffering from Major Depressive Disorder, which is characterized by episodes of low mood, poor self attitude and poor vitality. Of those suffering from Major Depressive Disorder (MDD), only one third completely improve, but even among these cases, there is a waiting period of several weeks or more during which antidepressants take effect. Our inability to adequately treat MDD is evident in its being ranked number one in Disability Adjusted Life Years (DALY) among persons aged 15-44. Given this profound burden, improving our understanding of the molecular basis of MDD is of utmost importance in the development of novel antidepressant medications. Serotoninergic neurotransmission is implicated in MDD, as demonstrated by the relative success of selective serotonin reuptake inhibitors (SSRIs). SSRIs block the reuptake of serotonin through the serotonin transporter, which then increases serotonin at the synaptic cleft. Serotonin then binds to 5-HT(1A) receptors, which are G-protein coupled receptors that are present both presynaptically and postsynaptically. Presynaptically, these receptors act as autoinhibitory receptors, triggering decreased firing rates and decreased serotonin release. This autoinhibitory mechanism is believed to be the reason why patients experience a delay in symptomatic improvement after initiation of SSRIs. Serotonin binding to postsynaptic receptors mediates symptomatic improvement of depression. Multiple positron emission tomography (PET) studies on 5-HT(1A) have been published. However, none of these studies use 5-HT(1A) agonists, which are specific for the high affinity, G-protein coupled and active state of the 5-HT(1A) receptor. We would therefore like to establish the use of the 5-HT(1A) radiolabelled agonist, \[(11)C\]CUMI, here at NIH. The purpose of this study is to perform whole body PET studies in healthy volunteers in order to estimate radiation absorbed doses for \[(11)C\]CUMI. Future experiments will include studies on Major Depressive Disorder.