Poster: The Effect of Traumatic Stress on the Mu-Opioid Receptors and Connectivity Within Reward Circuits, Negin Mohammadmirzaei

Post-traumatic stress disorder (PTSD) is often comorbid with opioid use disorder (OUD), but neurobiological mechanisms through which trauma exposure increases the susceptibility to OUD are under-examined. Changes in the mu-opioid receptor (MOR) function and connectivity among nodes in reward circuit are characteristic of OUD. Traumatic stress exposure may have similar effects on MORs and functional connectivity. This could be a mechanism via which traumatic stress leads to OUD susceptibility. Single prolonged stress (SPS) was used to examine the effect of traumatic stress on MOR function and functional connectivity in reward circuits including the medial prefrontal cortex (mPFC), amygdala (Amy), dorsal and ventral hippocampus (DH and VH), nucleus accumbens (NAc), and ventral tegmental area (VTA). Immunohistochemistry (IHC), western blot (WB), and ELISA was used to assay MOR function. Resting-state functional connectivity analyses using a 9.4T Brucker magnet was used for connectivity analyses. Our data showed a significant decrease in total MOR expression in the anterior cingulate cortex (ACC) of the mPFC following SPS exposure. Furthermore, SPS caused a significant increase in the internalization of MORs in the DH coupled with a significant decrease in the cytoplasmic MORs in the Amy. While the study is ongoing, preliminary results suggest that SPS exposure alters the MOR expression in the nodes of the reward circuit. The altered expression of MORs with SPS exposure, may contribute to increased vulnerability to development of OUD. While previous studies have shown that PTSD increases the susceptibility for OUD, the underlying neurobiological mechanisms remain unexplored. The results of our study will help address this gap.