PROJECT SUMMARY/ABSTRACT The opioid epidemic is a critical public health crisis in the United States; over 100 Americans die each day from an opioid overdose. To date, there are few effective treatments for individuals suffering from opioid use disorder. Critically, there is considerable data that demonstrates that men and women differ on opioid use characteristics. For example, women appear to progress more quickly from initial use to problematic use than men. Although this and other sex differences in opioid use characteristics have been reported, neuroimaging studies of opioid abusers have been mostly limited to males. Additionally, human neuroimaging studies have examined functional connectivity after chronic opioid exposure; thus, it is unclear if baseline differences in brain connectivity predict opioid misuse. This project addresses these unanswered questions by examining sex differences in neural mechanisms that underlie opioid use. We will examine circuitry-based changes utilizing resting-state functional magnetic resonance imaging (rsfMRI) in awake, non-anesthetized mice. This method allows for the longitudinal assessment of brain activity and drug behaviors in the same animal. In Aim 1, adult male and female C57BL/6J mice will undergo rsfMRI to characterize baseline resting-state functional connectivity (RSFC). Mice will then be allowed to voluntarily consume morphine. These data will allow us to determine if RSFC is a biomarker capable of predicting an individual’s vulnerability to initial opioid consumption. In Aim 2, the same mice will have a second rsfMRI to characterize post-drug RSFC. These data will allow us to determine if there are sex differences in morphine-induced changes in RSFC. The long-term goal of this work is to develop targeted treatments that could aid individuals suffering from opioid use disorder.

PROJECT NARRATIVE Over 100 Americans lose their lives to the opioid epidemic each day, demonstrating that this is a critical public health topic. Results from this project will provide an understanding of how brain function relates to opioid consumption. These data have the potential to lead to the development of improved treatments for individuals who suffer from an opioid use disorder.