Opioid withdrawal behavior in spiny mice: A novel preclinical model of neonatal opioid withdrawal syndrome (NOWS)

Abstract

As the opioid epidemic continues to grow, opioid use among pregnant women is increasing significantly. This has led to a steady rise in the number of infants born with neonatal opioid withdrawal syndrome (NOWS). Although short-term withdrawal symptoms associated with NOWS are well characterized, there are many gaps in our understanding of the short and long-term effects of prenatal opioid exposure. Current animal models of NOWS are limited by shortened gestational periods, large litter sizes, and primary organogenesis occurring after birth. This often leads to postnatal treatment to mimic drug exposure during third-trimester development. Using the unique rodent species Acomys cahirinus, more commonly known as spiny mice, which have an extended 40-day gestation period, small litter sizes, and increased in utero organogenesis we aim to study the short-term effects of prenatal morphine exposure by assessing withdrawal behavior. To model maternal opioid use, dams were treated daily with morphine (10 and 30 mg/kg S.C.) beginning on gestation day 19 until the day of birth; this resulted in a cumulative exposure of 19–21 days. Withdrawal behaviors for each pup were recorded daily between postnatal days 0–7 (PND 0–7). Our study found that prenatal morphine exposure in spiny mice led to an increase in withdrawal behavior throughout the early postnatal period and validated the use of this species as a novel pre-clinical model of NOWS. We are hopeful this rodent model will further our understanding of the short and long-term consequences of prenatal opioid exposure on neurodevelopment and behavior.