From morphine to buprenorphine - Modeling opioid use disorder and its treatment during pregnancy: Effects on maternal care and offspring neurodevelopment in a translational rodent model.

Opioid use during pregnancy has increased drastically in the last two decades. Pregnant women who use opioids are often prescribed Medications for Opioid Use Disorder (MOUDs), including buprenorphine (BUP), to mitigate negative effects on the fetus. However, BUP exposure during pregnancy may still negatively impact maternal care behavior and offspring neurodevelopment. In the current study, we used a translational rodent model to investigate the effects of continued morphine or BUP use from preconception (7 days prior to mating) to the early postpartum period, as well as the transition from morphine to BUP during early pregnancy (gestational day (GD) 5), on both maternal care behaviors and acute offspring neurodevelopmental outcomes. Our results reveal that exposure to BUP beginning before pregnancy or on GD5 resulted in decreased nesting quality, maternal motivation, and pup-directed care behaviors as compared to controls. For the offspring, BUP-exposure resulted in increased pup mortality, more neonatal opioid withdrawal syndrome-like (NOWS) symptoms, altered norepinephrine levels in the brain, and decreased offspring weight, body length, and presence of milk bands compared to vehicle pups. Importantly, maternal care behavior was significantly correlated with offspring mortality, physical maturation, and NOWS-like scores, suggesting that at least some of the adverse effects were driven by impairments in maternal care. Morphine-exposed dams and pups showed overall fewer impairments compared to BUP-exposed dams and pups. This highlights that more research is needed to further understand the unique impact of BUP on the maternal brain and subsequent infant outcomes to mitigate potential adverse effects in pregnant women with MOUD prescriptions.