Developmental exposure to 17-α-hydroxyprogesterone caproate disrupts decision-making in adult female rats: A potential role for a dopaminergic mechanism

Paige L Graney; Michael Y Chen; Ruth I Wood; Christine K Wagner

doi:10.1016/j.yhbeh.2024.105550

Developmental exposure to 17-α-hydroxyprogesterone caproate disrupts decision-making in adult female rats: A potential role for a dopaminergic mechanism

Horm Behav. 2024 Apr 25:163:105550. doi: 10.1016/j.yhbeh.2024.105550. Online ahead of print.

Authors

Paige L Graney¹, Michael Y Chen², Ruth I Wood³, Christine K Wagner⁴

Affiliations

¹ Department of Psychology & Center for Neuroscience Research, University at Albany, Albany, NY, USA. Electronic address: pgraney@albany.edu.
² Department of Integrative Anatomical Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; Western University of Health Sciences, Pomona, CA, USA.
³ Department of Integrative Anatomical Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
⁴ Department of Psychology & Center for Neuroscience Research, University at Albany, Albany, NY, USA.

PMID: 38669977
DOI: 10.1016/j.yhbeh.2024.105550

Abstract

The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to pregnant individuals at risk for preterm birth and is likely transferred from mother to fetus. Yet, there is little information regarding the potential effects of 17-OHPC administration on behavioral and neural development in offspring. In rats, neonatal 17-OHPC exposure altered dopaminergic fiber distribution and density in the prelimbic medial prefrontal cortex (mPFC) in neonates and adolescents, respectively. Additionally, neonatal 17-OHPC exposure in male rats increased response omissions in a delay discounting task of impulsive decision-making. Because developmental 17-OHPC exposure has differential effects in males and females, investigating the effects of 17-OHPC on impulsive decision-making in female rats is necessary. The present study tested the effects of developmental 17-OHPC exposure (P1-P14) in a delay discounting task in which female rats chose between a small immediate reward and a larger delayed (0, 15 30, or 45 s) reward. 17-OHPC-exposed females made more omissions than controls. There was no effect of 17-OHPC on large reward preference nor on response time, and omissions were similar during both free- and forced-choice trials. The present study also aimed to investigate the neural mechanisms underlying omissions in 17-OHPC-exposed female rats. The dopamine transporter inhibitor, methylphenidate (MPH), was administered prior to delay discounting testing. MPH treatment did not reduce omissions in 17-OHPC-exposed females. If anything, MPH increased omissions in control females nearly fourfold during the longest delays. These results suggest that developmental 17-OHPC exposure increased omissions without affecting impulsivity or slowing decision-making. Furthermore, omissions may be regulated, at least in part, by dopaminergic mechanisms.

Keywords: 17-OHPC; Delay-discounting; Development; Methylphenidate; Omissions; Progestins.