PROJECT SUMMARY/ABSTRACT The Center of Research Excellence in Natural Products Neuroscience (CORE-NPN) at The University of Mississippi School of Pharmacy (UM), initiated ten years ago through a COBRE grant, has developed a multidisciplinary team committed to evaluating the effects of natural products on the central nervous system (CNS). The Neuropharmacology Research Core of the COBRE CORE-NPN program represents a shared resource serving biomedical investigators / users with specialized services and training in neuropharmacological bioassays based on (a) competitive radioligand receptor binding, (b) modulation of molecular/biochemical target functions (c) cell-based phenotypic & functional responses and (d) in vivo behavioral pharmacology. This was originally two Cores, in vitro and in vivo pharmacology, in Phases I and II, with strong utilization by investigators and strong collaboration between the two. In Phase III, it has been determined that these Cores would best serve the program as one functional unit. Furthermore, by the end of Phase III, the Core is projected to be largely sustainable with efforts focused on understanding neuropharmacological properties of lead biological extracts or purified compounds and how they interact with biological systems. Efforts have been focused on expanding the core capabilities by increasing both in vitro and in vivo assays that are available to users, thereby increasing the numbers of projected users served. A fee-for-service/chargeback business model will be implemented during Phase III to ensure sustainability post Phase III. Specific Core services include radioligand binding and functional assays for cannabinoid, opioid, and Neuropeptide FF G protein-coupled receptors (GPCRs), as well as enzyme assays, phenotypic neuronal cell cultures-based assays, and analysis of neuropharmacological signaling pathways. Moreover, the Core offers a battery of acute behavioral rodent and zebrafish assays to evaluate natural product extracts and purified compounds in vivo. New in vitro assays and animal models will continue to be developed to support user needs, which ultimately broadens the overall scope and user-base for the Core. The Core is positioned to become a leader in neuropharmacological services based on natural product and synthetic drug development campaigns. We plan to achieve this through the following Specific Aims: 1) To enhance the research of the COBRE CORE-NPN and the associated community through state-of-the-art equipment, cutting-edge techniques, and scientific expertise; 2) To advance an infrastructure of developmental services to facilitate COBRE CORE-NPN research and the associated community by continual refinement and addition of assays through user input. 3) To accelerate a long-term plan for sustainability of the Core through expansion of the user base, integration of a fee-for-service structure, institutional support, and adaptation to changes by monitoring the needs of the users.