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Access Type
WSU Access
Date of Award
January 2024
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Psychology
First Advisor
Scott E. Bowen
Second Advisor
Susanne Brummelte
Abstract
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 on maternal care behavior and offspring neurodevelopment. Further, it is not known how the transition from an opioid of abuse (i.e., morphine) to a MOUD (i.e., BUP) during gestation affects maternal and offspring outcomes. In the current study, we used a translational rodent model to investigate acute offspring neurodevelopmental outcomes following either the transition from morphine to BUP or continued use of morphine or BUP from preconception (7 days prior to mating) to the early postpartum period. Dams were assigned to one of 5 experimental groups: BUP continued (BC, 1 mg/kg, s.c.), morphine continued (MC, 3 – 10 mg/kg, s.c.), morphine to BUP (MB; 3-5 mg/kg morphine until Gestational Day (GD) 5, then 1.0 mg/kg BUP; s.c.), morphine to vehicle (MV; 3-5 mg/kg morphine until GD5, then 1.0 mL/kg saline; s.c.), or saline continued (VEH, 1.0 mL/kg, s.c.). MB and MV groups switched to BUP or saline (respectively) on GD5 to roughly mimic the time in humans when a woman would discover she is pregnant (i.e. ~ 6-8 weeks of pregnancy). All dams and their litters were sacrificed on postnatal day (PN) 2. Continuous exposure to BUP or morphine and the transition from morphine to BUP resulted in higher pup mortality, lower pup body weight, smaller pup body length, fewer milk bands, and more NOWS symptoms as compared to controls. Additionally, MB damns partook in significantly less pup-directed maternal care behaviors than drug-naïve dams, potentially contributing to the high pup mortality rate. Importantly, maternal care behavior was significantly correlated with offspring mortality, physical maturation and NOWS scores. Pup brains collected on PN2 showed lower norepinephrine (NE) in the prefrontal cortex and higher NE in the striatum of opioid-exposed pups. These results suggest that (1) the transition from morphine to BUP in early pregnancy and continued use of BUP or morphine negatively impacts offspring outcomes and alters early neurochemistry and (2) opioid-induced maternal care deficits appear to contribute to offspring neurodevelopmental outcomes following opioid exposure in utero.
Recommended Citation
Myers, Abigail, "Transitioning From Morphine To Buprenorphine During Pregnancy: Effects On Maternal Care And Offspring Neurodevelopment In A Translational Rodent Model" (2024). Wayne State University Dissertations. 3976.
https://digitalcommons.wayne.edu/oa_dissertations/3976
