Consequences of fentanyl self-administration during pregnancy

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ABSTRACT Opioid abuse of pregnant women or women of childbearing age in general is an urgent public health concern. The number of women using opioids presenting at labor and delivery has more than quadrupled in the last decade. While the imminent effects of opioid use during pregnancy, namely neonatal opiate withdrawal syndrome, are well described, there is only limited knowledge about the long-term harmful effect of opioid abuse during pregnancy on the developing child. This proposal aims to investigate the effects of prenatal fentanyl exposure, and its short- and long-term consequences on the offspring – from infancy through adulthood- using a translationally relevant approach in which rat dams self-administer fentanyl intravenously under extended- access conditions prior and throughout pregnancy. In one specific Aim we will test the hypothesis that daily extended-access to intravenous fentanyl self-administration constitutes a translationally relevant model of fentanyl abuse on pregnant women, that induces neonatal opioid withdrawal, impaired offspring development, and altered sensitivity to opiates that persists throughout adulthood. We will assess comprehensively the overall health, occurrence and severity of neonatal opiate withdrawal and achievement of age-appropriate somatic and behavioral developmental milestones by the offspring, followed by evaluation of sensitivity to opiates. In comparison to pups from yoked saline control dams, we expect that prenatal fentanyl exposure will lead to delayed achievement of developmental milestones, and increased sensitivity to fentanyl, and we expect the severity of deficits will be directly related to level of fentanyl exposure. In addition, we expect that improved maternal care, as achieved by cross-fostering of litters between fentanyl and saline dams, will ameliorate the observed developmental effects. The results from the proposed studies will provide needed information regarding the role of fentanyl exposure itself, the presence/severity of opioid withdrawal and altered maternal care in the persistent physical and behavioral impairment of pups exposed to fentanyl. Ultimately, our studies should lead to knowledge that is vital for the identification of treatment opportunities, both pre- and postpartum.