Prenatal opioid exposure inhibits microglial sculpting of the dopamine system during adolescence

The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. However, little is know about the mechanisms by which prenatal opioid exposure leads to long term changes in reward circuit function and behavior. Microglia, the resident immune cells of the brain, are known to respond to perinatal opioid exposure and to sculpt neural circuits during development. Indeed, we recently found that microglial phagocytosis of dopamine D1 receptors in the nucleus accumbens (NAc) is required for the natural developmental decline in NAc-D1R that occurs between adolescence and adulthood. Morever, this microglial pruning occurs only in males, and is required for the normal developmental trajectory of social play behavior. Here, we show that maternal oxycodone self-administration during pregnancy leads to higher D1R density within the NAc in adult male, but not female, offspring in rats. Furthermore, adolescent microglial phagocytosis of D1R is reduced following prenatal oxycodone exposure. This work demonstrates for the first time that microglia play a key role in translating prenatal opioid exposure to long-term changes in neural systems. HighlightsO_LIPrenatal opioid exposure decreases offspring body weight in males and females C_LIO_LIPrenatal opioid exposure does not alter D2 receptor or Tyrosine Hydroxylase fiber density in either sex C_LIO_LIPrenatal opioid exposure increases nucleus accumbens dopamine D1 receptor expression in males but not females C_LIO_LIPrenatal opioid exposure decreases microglial phagocytosis of D1R in the nucleus accumbens in males only C_LI