Perinatal opioid exposure leads to decreased social play in adolescent male and female rats: Potential role of oxytocin signaling in brain regions associated with social reward

Over the last two decades, the number of infants exposed to opioids in utero has quadrupled in the United States, with some states reporting rates as high as 55 infants per 1000 births. Clinical studies report that children previously exposed to opioids during gestation show significant deficits in social behavior, including an inability to form friendships or other social relationships. To date, the neural mechanisms whereby developmental opioid exposure disrupts social behavior remain unknown. Using a novel paradigm of perinatal opioid administration, we tested the hypothesis that chronic opioid exposure during critical developmental periods would disrupt ju-venile play. As oxytocin is a major regulator of sociability, the impact of perinatal morphine exposure on oxytocin peptide expression was also examined. Juvenile play was assessed in vehicle-or morphine-exposed male and female rats at P25, P35, and P45. Classical features of juvenile play were measured, including time spent engaged in social play, time not in contact, number of pins, and number of nape attacks. We report that morphine-exposed males and females spend less time engaged in play behavior than control males and females, with a corresponding increase in time spent alone. Morphine-exposed males and females also initiated fewer pins and nape attacks. Together, these data suggest that male and female rats exposed to morphine during critical developmental periods are less motivated to participate in social play, potentially due to alterations in oxytocin-mediated reward signaling.