Prenatal opioid exposure inhibits microglial sculpting of the dopamine system selectively in adolescent male offspring.
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
18
01
2022
accepted:
25
06
2022
revised:
22
06
2022
pubmed:
15
7
2022
medline:
16
8
2022
entrez:
14
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35835992
doi: 10.1038/s41386-022-01376-4
pii: 10.1038/s41386-022-01376-4
pmc: PMC9372181
doi:
Substances chimiques
Analgesics, Opioid
0
Receptors, Dopamine D1
0
Oxycodone
CD35PMG570
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1755-1763Subventions
Organisme : NIDA NIH HHS
ID : K00 DA053527
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
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