RT Journal Article
SR Electronic
T1 Enduring consequences of perinatal fentanyl exposure in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 735464
DO 10.1101/735464
A1 Jason B. Alipio
A1 Adam T. Brockett
A1 Megan E. Fox
A1 Stephen S. Tennyson
A1 Coreylyn A. deBettencourt
A1 Dina El-Metwally
A1 Nikolas A. Francis
A1 Patrick O. Kanold
A1 Mary Kay Lobo
A1 Matthew R. Roesch
A1 Asaf Keller
YR 2019
UL http://biorxiv.org/content/early/2019/08/15/735464.abstract
AB Opioid use by pregnant women is an understudied consequence associated with the opioid epidemic, resulting in a rise in the incidence of neonatal opioid withdrawal syndrome (NOWS), and lifelong neurobehavioral deficits that result from perinatal opioid exposure. There are few preclinical models that accurately recapitulate human perinatal drug exposure, and none focus on fentanyl, a potent synthetic opioid that is a leading driver of the opioid epidemic. To more readily investigate the consequences of perinatal opioid exposure, we administered fentanyl to mouse dams in their drinking water throughout gestation and until litters are weaned at postnatal day (PD) 21. First, we found that fentanyl-exposed dams delivered smaller litters, when compared to saccharine-exposed control dams. Twenty-four hours after weaning and drug cessation, fentanyl-exposed mice exhibited signs of somatic withdrawal, and sex-specific weight fluctuations that normalized in adulthood. At adolescence (PD 35) they displayed elevated anxiety-like behaviors and decreased grooming, assayed in the elevated plus maze and sucrose splash tests. Finally, in adulthood (PD 55) they displayed impaired performance in a two-tone auditory discrimination task. Collectively, our findings suggest that we have developed an effective rodent model of NOWS, with high face validity that will allow studying changes associated with perinatal fentanyl exposure across the lifespan.