Numerous lines of evidence reviewed in the introduction of this CCNMD sugges(that alterations of dopamine (DA) neurotransmission are associated with schizophrenia. Recent development of methods to assess DA neurotransmission in vivo with PET allows direct testing of this hypothesis in patients. The Brain Imaging Core is an integrated team of scientists from various disciplines (chemistry, pharmacology, physics, mathematics), covering the range of expertise needed to develop and support PET neuroreceptor and mouse MRI studies. The services provided to the Center by the Brain Imaging Core fall into three general categories:1) To provide logistical support and technical expertise to brain imaging projects of the Center. The Core provides expertise at the level of study design, implementation, and analysis. In addition, these studies benefit from the general infrastructure maintained by the Core, such as radiochemistry and image analysis laboratories.2) To provide training in brain imaging to young investigators. These include young psychiatrists, who are completing a fellowship in the Division of Functional Brain Mapphng as Well as other investigators in the Center who are interested in applying brain imaging techniques to the study of schizophrenia. 3) To develop new imaging modalities that are pertinent to schizophrenia research. Over the next five years, our efforts will be targeted at examining the DA and glutamate systems with PET. We will focus on the following objectives, guided by a general model of neurochemical imbalance associated with schizophrenia described in the Introduction to the Center. a) To continue the characterization of the in vivo properties of the D2 agonist we have radiolabeled; b) To develop a new D1 receptor radiotracer whose binding is affected by acute fluctuations in endogenous DA; c) To develop a radiotracer that labels the NR2B site of the NMDA methods we have applied in other settings to the mouse models of schizophrenia explored in several of the Projects, and f) to continue to refine the voxelwise kinetic modeling methods we have developed.Together, these projects should provide new and sophisticated tools for the study of schizophrenia. The radiotracers and methods developed during this funding cycle of the Center will be made available to the scientific community.
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