Prenatal fentanyl exposure affects social dominance and myelination patterns in the adult mouse brain

Fentanyl use has reached epidemic proportions, and more adults are administering the drug illicitly. Despite its high use rates, very little is known of the long-term effects following prenatal fentanyl exposure. Using an oral model of lower-dose prenatal fentanyl administration in mice, we found that fentanyl-exposed offspring developed similarly to their saline-exposed counterparts. In adulthood, there were few significant changes in tests of anxiety- and depression-like behavior, cognition, or ambulatory function. However, fentanyl-exposed mice, specifically males, exhibited significant deficits in social dominance and social interaction. RNA sequencing of the amygdala and subsequent examination of myelin basic protein levels suggested that prenatal fentanyl exposure affects myelin-related processes, which may impact the subsequent behavioral changes. These data suggest that in utero fentanyl exposure could significantly alter social-related behaviors, which may be related to aberrant brain myelination and connectivity.