Dietary Supplementation with Omega-3 Fatty Acids Rescues Neurodevelopmental Deficits in a Combined Exposure Paradigm of Maternal Oxycodone Exposure and Chronic Stress.

In recent years, opioid abuse has become a major public health crisis affecting millions of individuals throughout the world. This widespread abuse of prescription opioids and dramatic increase in their availability have created the opioid epidemic. Further, oxycodone (oxy), which is prescribed for multiple types of pain, is gaining momentum as a pain reliever in pregnant women. Whilst successful in inducing analgesia, oxy freely passes through the placenta and can impact the overall development of the fetus in major ways. Currently, mechanisms that lead to impairment in the exposed offspring, including identification of biomarkers, are not well described. To fill this gap, our study utilizes a preclinical rodent model to test the therapeutic efficacy of omega-3 fatty acids (O3FA) in attenuating neurodevelopmental deficits in offspring exposed to chronic stress (CS) and oxy in utero which mirrors real-world cases of opioid use during pregnancy co-occurring with chronic psychosocial stress. Our results show that O3FA supplementation partially rescues phenotypic, biochemical, molecular, and behavioral endpoints. Notably, our proteomic study identified distinct key synaptic signatures, including functional pathways impacted in different treatment groups. Furthermore, RT-qPCR results identified key inflammatory markers whose expression was ameliorated by O3FA supplementation. Together, this study bridges an important knowledge gap pertinent to maternal-fetal health that reflects a combined exposure of oxy and CS that is clinically relevant and enumerates the therapeutic efficacy of O3FA in mitigating neurodevelopmental deficits in offspring exposed to in utero oxy and CS.