We propose to establish a Center of Excellence for Addiction Studies (CEAS) that will offer core services allowing users to develop projects that will lead to new research in addiction. Addiction and relapse are characterized by dysregulation of brain circuitry that involves diminished activity of brain reward circuits, increased responsiveness of stress circuits and impaired functioning of executive cortical circuits. Neural changes are observed in the basal ganglia, extended amygdala and prefrontal cortical regions and encompass a wide range of endogenous neurotransmitters including dopamine, opioid peptides, endocannabinoids, corticotropin releasing factor (CRF), dynorphin, glutamate and others. While chronic pain and addiction are different disorders, there is a remarkable overlap between the influence of drugs of abuse and chronic pain on these circuits. Our faculty has broad expertise in evaluation of mechanisms that underlie the maladaptations promoted by pain in these circuits. The CEAS will be composed of four Cores and a Pilot Research Project. The Administrative Core will provide the structural elements that will allow efficient functioning of the CEAS. The Genetic Targeting of Neural Circuits Core will allow users to employ cutting edge genetic techniques including CRISPR/Cas9 gene editing, chemogenetics and optogenetics to produce cell and circuit-specific manipulations to evaluate potential mechanisms relevant to addiction. The Neuroanalytical Core will provide users with advanced methods of measuring neurotransmitters with temporal resolution spanning milli-seconds to days and with spatial specificity through advanced detection methods. The Behavioral Core will allow users to explore questions relevant to addiction using behavioral assays that evaluate addictive processes including the influence of addictive drugs on cognitive function. Investigators in the CEAS have worked together for many years and have shared and individual research funding. Additionally, the CEAS will offer opportunities for other investigators at University of Arizona as well as Arizona State University, Northern Arizona University, The University of New Mexico and Texas Tech University Health Sciences Center at Lubbock and El Paso establishing a Southwestern region engaged in addiction sciences. The CEAS will promote increased diversity in addiction research by recruiting investigators and students from under-represented populations in neuroscience and addiction. The impact of the CEAS will be to leverage established funding to develop new research on addiction research. In addition, the impact of funds from the CEAS will be amplified by commitments of matching funds from the University of Arizona and from a recently established Comprehensive Center of Pain and Addiction. The CEAS will provide key services to its users that correspond with the goals of the NIDA to enhance addiction research with a goal of development of therapies that can stem the opioid epi...