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

• Published in: Hormones and behavior 2024-07, Vol.163, p.105550, Article 105550
• Main Authors: Graney, Paige L., Chen, Michael Y., Wood, Ruth I., Wagner, Christine K.
• Format: Article
• Language: English
• Subjects: 17 alpha-Hydroxyprogesterone Caproate; 17-OHPC; Animals; Animals, Newborn; Decision Making - drug effects; Delay Discounting - drug effects; Delay-discounting; Development; Dopamine - metabolism; Female; Impulsive Behavior - drug effects; Methylphenidate; Omissions; Prefrontal Cortex - drug effects; Pregnancy; Progestins; Rats; Rats, Sprague-Dawley; Reward
• ISSN: 0018-506X; 1095-6867; 1095-6867
• DOI: 10.1016/j.yhbeh.2024.105550

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. •17-OHPC-exposed rats committed more omissions in a delay-discounting task.•Omissions were not a result of slowed response time.•Developmental 17-OHPC exposure had no effect on impulsivity in female rats.•Methylphenidate had no effect on impulsivity or response time in either group.•17-OHPC-exposed and control females responded to Methylphenidate differently.