Developmental exposure to 17α-hydroxyprogesterone caproate impairs adult delayed reinforcement and reversal learning in male and female rats.
Developmental exposure to 17α-hydroxyprogesterone caproate impairs adult delayed reinforcement and reversal learning in male and female rats.
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DOI：
10.1111/jne.12862
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发表时间：
2020-06
影响因子：
3.2
通讯作者：
Wood RI
中科院分区：
文献类型：
--
作者：
Serpa RO;Wagner CK;Wood RI
有不明原因流产史的妇女在妊娠中期经常使用合成黄体酮17α-羟孕酮己酸酯（17-OHPC）。然而，人们对17-OHPC的长期行为影响知之甚少。对啮齿动物的研究表明，发育中的大脑对黄体酮很敏感。新生儿17-OHPC损害成人在设定转移和延迟折扣方面的表现。本研究测试了17-OHPC （0.5 mg kg - 1）或从出生后1 - 14天起给药对成年大鼠认知功能的影响。通过对糖丸的操作性反应、延迟强化或逆转学习的测量来评估男性和女性的认知功能（每组8-10人）。对于延迟强化，大鼠在对杠杆做出反应后必须等待15秒才能获得弹丸。延迟用灯表示或不表示。对于反向学习，大鼠必须在有刺激光的杠杆上做出反应，然后学习在没有刺激光的杠杆上做出反应。对于延迟强化，大鼠在有信号条件下比没有信号条件下获得更多的颗粒。同样，与雌性相比，雄性做出了更多的反应，获得了更多的颗粒。在信号条件下，17- ohpc治疗的大鼠获得的颗粒比对照组少。对于逆向学习，结果是相似的。雌性比雄性需要更多的试验才能对新规则做出正确的反应，而17- ohpc治疗的大鼠比对照组需要更多的试验。这表明在发育过程中暴露于17-OHPC可能会损害认知功能。考虑到对17-OHPC预防流产的有效性提出的问题，可能有必要重新考虑怀孕期间使用黄体酮治疗。
Women with a history of unexplained miscarriage are frequently prescribed the synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC) during the middle trimester of pregnancy. However, little is known about the long-term behavioural effects of 17-OHPC. Work in rodents suggests that the developing brain is sensitive to progestins. Neonatal 17-OHPC impairs adult performance in set-shifting and delay discounting. The present study tested the effects of 17-OHPC (0.5 mg kg−1) or vehicle administration from postnatal days 1–14 on cognitive function in adulthood in rats. Cognitive function was assessed in males and females (n = 8–10 per group) by operant responding for sugar pellets, measuring delayed reinforcement or reversal learning. For delayed reinforcement, the rat must wait 15 seconds for pellets after responding on a lever. Delay is signalled by a light or is unsignalled. For reversal learning, the rat must respond on the lever under a stimulus light, and then learn to respond on the unlit lever. For delayed reinforcement, rats earned more pellets under signalled vs unsignalled conditions. Likewise, males made more responses and earned more pellets compared to females. Under signalled conditions, 17-OHPC-treated rats earned fewer pellets than controls. For reversal learning, the results were similar. Females required more trials than males to respond correctly for the new rule, and 17-OHPC-treated rats required more trials than controls. This suggests that 17-OHPC exposure during development may impair cognitive function. Considering that questions have been raised as to the efficacy of 17-OHPC to prevent miscarriage, it may be necessary to rethink the use of progestin therapy during pregnancy.
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