We propose to establish a Center of Excellence for Addiction Studies (CEAS) that will offer core services allowingusers to develop projects that will lead to new research in addiction. Addiction and relapse are characterized bydysregulation of brain circuitry that involves diminished activity of brain reward circuits increased responsivenessof stress circuits and impaired functioning of executive cortical circuits. Neural changes are observed in the basalganglia extended amygdala and prefrontal cortical regions and encompass a wide range of endogenousneurotransmitters including dopamine opioid peptides endocannabinoids corticotropin releasing factor (CRF)dynorphin glutamate and others. While chronic pain and addiction are different disorders there is a remarkableoverlap between the influence of drugs of abuse and chronic pain on these circuits. Our faculty has broadexpertise in evaluation of mechanisms that underlie the maladaptations promoted by pain in these circuits. TheCEAS will be composed of four Cores and a Pilot Research Project. The Administrative Core will provide thestructural elements that will allow efficient functioning of the CEAS. The Genetic Targeting of Neural CircuitsCore will allow users to employ cutting edge genetic techniques including CRISPR/Cas9 gene editingchemogenetics and optogenetics to produce cell and circuit-specific manipulations to evaluate potentialmechanisms relevant to addiction. The Neuroanalytical Core will provide users with advanced methods ofmeasuring neurotransmitters with temporal resolution spanning milli-seconds to days and with spatial specificitythrough advanced detection methods. The Behavioral Core will allow users to explore questions relevant toaddiction using behavioral assays that evaluate addictive processes including the influence of addictive drugson cognitive function. Investigators in the CEAS have worked together for many years and have shared andindividual research funding. Additionally the CEAS will offer opportunities for other investigators at Universityof Arizona as well as Arizona State University Northern Arizona University The University of New Mexico andTexas Tech University Health Sciences Center at Lubbock and El Paso establishing a Southwestern regionengaged in addiction sciences. The CEAS will promote increased diversity in addiction research by recruitinginvestigators and students from under-represented populations in neuroscience and addiction. The impact of theCEAS will be to leverage established funding to develop new research on addiction research. In addition theimpact of funds from the CEAS will be amplified by commitments of matching funds from the University of Arizonaand from a recently established Comprehensive Center of Pain and Addiction. The CEAS will provide keyservices to its users that correspond with the goals of the NIDA to enhance addiction research with a goal ofdevelopment of therapies that can stem the opioid epidemic as well as impacting other substance abusedisorders. The close collaboration between the Cores ensures high expertise in all areas of the addictionresearch and will permit outcome measures emphasizing scientific rigor and reproducibility.