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Date of Award
Scott E. Bowen
The recent opioid crisis in the US lead to an increase in women being treated with opioid maintenance therapy (such as buprenorphine), which in turn resulted in an increase of infants who are/were exposed to opioids in utero. However, there is still a dearth of knowledge regarding developmental consequences following gestational buprenorphine exposure, especially in regards to preconceptional exposure. Though the fetal opioid system is still immature shortly after conception, the mother’s physiological response to drug is critical and can differ significantly between a new and established user. Thus, our animal (rodent) model is representative of an established user by starting buprenorphine exposure 7 days prior to conception and continuing administration throughout the postpartum period. Our results reveal that dams exposed to a low dose (0.3 mg/kg) of buprenorphine displayed subtle effects on dams but reduced some maternal behavior. Subsequent low-dose exposed offspring expressed developmental deficits and altered pain sensitivity. Dams exposed to a high dose (1mg/kg) buprenorphine gained less maternal weight and a majority of dams ceased performance of basic maternal care which may have accounted for excessive rates of mortality. High-dose exposed offspring displayed significant neonatal opioid withdrawal symptoms at postnatal day (PN) 2 and may be responsible for deficits seen in maturation and development. Our data support the therapeutic potential of low dose buprenorphine but caution against the use of buprenorphine in high doses (over exposure). Further analysis of collected tissue will reveal whether physiological alterations are associated with behavioral changes. Our future work will assess developmental differences in offspring born to mothers chronically exposed to commonly abused opiates (morphine/oxycodone) that transition to an approved opioid maintenance therapy (buprenorphine) after conception.
Wallin, Chela M., "Gestational Opioid Exposure: Effects On Pregnancy, Neonatal Abstinence Syndrome, Maturation & Behavioral Development" (2019). Wayne State University Theses. 725.