Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring.

Autor: Smith CJ; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA. Caroline.j.smith@duke.edu., Lintz T; Department of Psychiatry, Harvard Medical School and Basic Neuroscience Division, Mclean Hospital, Belmont, MA, USA., Clark MJ; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA., Malacon KE; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA., Abiad A; Department of Psychiatry, Harvard Medical School and Basic Neuroscience Division, Mclean Hospital, Belmont, MA, USA., Constantino NJ; Department of Psychiatry, Harvard Medical School and Basic Neuroscience Division, Mclean Hospital, Belmont, MA, USA., Kim VJ; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA., Jo YC; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA., Alonso-Caraballo Y; Department of Psychiatry, Harvard Medical School and Basic Neuroscience Division, Mclean Hospital, Belmont, MA, USA., Bilbo SD; Department of Psychology and Neuroscience, Duke University, Durham, NC, USA., Chartoff EH; Department of Psychiatry, Harvard Medical School and Basic Neuroscience Division, Mclean Hospital, Belmont, MA, USA.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2022 Sep; Vol. 47 (10), pp. 1755-1763. Date of Electronic Publication: 2022 Jul 14.
DOI: 10.1038/s41386-022-01376-4
Abstrakt: The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. A number of social and cognitive abnormalities have been documented in these children as they reach young adulthood. However, little is known about the mechanisms underlying developmental effects of prenatal opioid exposure. Microglia, the resident immune cells of the brain, respond to acute opioid exposure in adulthood. Moreover, microglia are known to sculpt neural circuits during typical development. Indeed, we recently found that microglial phagocytosis of dopamine D1 receptors (D1R) in the nucleus accumbens (NAc) is required for the natural developmental decline in NAc-D1R that occurs between adolescence and adulthood in rats. This microglial pruning occurs only in males, and is required for the normal developmental trajectory of social play behavior. However, virtually nothing is known as to whether this developmental program is altered by prenatal exposure to opioids. Here, we show in rats that maternal oxycodone self-administration during pregnancy leads to reduced adolescent microglial phagocytosis of D1R and subsequently higher D1R density within the NAc in adult male, but not female, offspring. Finally, we show prenatal and adult behavioral deficits in opioid-exposed offspring, including impaired extinction of oxycodone-conditioned place preference in males. This work demonstrates for the first time that microglia play a key role in translating prenatal opioid exposure to changes in neural systems and behavior.
(© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)
Databáze: MEDLINE
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