Developmental exposure to the synthetic progestin, 17α-hydroxyprogesterone caproate, disrupts the mesocortical serotonin pathway and alters impulsive decision-making in rats.
delay discounting
medial prefrontal cortex
omissions
prelimbic
synaptophysin
Journal
Developmental neurobiology
ISSN: 1932-846X
Titre abrégé: Dev Neurobiol
Pays: United States
ID NLM: 101300215
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
20
07
2021
received:
14
04
2021
accepted:
23
07
2021
pubmed:
29
7
2021
medline:
1
4
2022
entrez:
28
7
2021
Statut:
ppublish
Résumé
The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to women at risk for preterm birth during a critical period of fetal development for mesocortical pathways. Yet, little information is available regarding the potential effects of 17-OHPC on the developing fetal brain. In rat models, the mesocortical serotonin pathway is sensitive to progestins. Progesterone receptor (PR) is expressed in layer 3 pyramidal neurons of medial prefrontal cortex (mPFC) and in serotonergic neurons of the dorsal raphe. The present study tested the hypothesis that exposure to 17-OHPC during development disrupts serotonergic innervation of the mPFC in adolescence and impairs behavior mediated by this pathway in adulthood. Administration of 17-OHPC from postnatal days 1-14 decreased the density of SERT-ir fibers within superficial and deep layers and decreased the density of synaptophysin-ir boutons in all layers of prelimbic mPFC at postnatal day 28. In addition, rats exposed to 17-OHPC during development were less likely to make impulsive choices in the Delay Discounting task, choosing the larger, delayed reward more often than controls at moderate delay times. Interestingly, 17-OHPC exposed rats were more likely to fail to make any choice (i.e., increased omissions) compared to controls at longer delays, suggesting disruptions in decision-making. These results suggest that further investigation is warranted in the clinical use of 17-OHPC to better inform a risk/benefit analysis of progestin use in pregnancy.
Identifiants
pubmed: 34318625
doi: 10.1002/dneu.22847
pmc: PMC8440456
mid: NIHMS1728250
doi:
Substances chimiques
Progestins
0
17 alpha-Hydroxyprogesterone Caproate
276F2O42F5
Serotonin
333DO1RDJY
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
763-773Subventions
Organisme : NICHD NIH HHS
ID : R01 HD093907
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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