PROJECT SUMMARY/ABSTRACT Opioid use within the US has reached epidemic proportions, negatively impacting not just individuals and their families, but also communities. One of the most affected populations is pregnant women and their exposed offspring. Despite efforts to reduce access to prescription opioids, more potent, synthetic analogs such as fentanyl are becoming more readily available. Little is known of the long-term effects of fentanyl in exposed children. In this proposal, we will develop a clinically relevant mouse model of prenatal fentanyl exposure to determine the pharmacokinetic and functional (behavioral) profiles in exposed offspring. Developmental opioids are known to affect specific behavioral domains, and we will test offspring at both early (neonatal) and late (adult) ages. We hypothesize that fentanyl will diminish performance of behaviors related to drug reward and addiction, cognition, affect, social outcomes, and motor coordination. We further posit that the route and duration of exposure will exacerbate these deficiencies. This study will be the first to examine how long-term developmental fentanyl exposure alters both short- and long-term functional outcomes and will position us to determine the critical neural circuit changes underlying these altered phenotypes in order to develop therapeutic approaches in exposed children