Developmental exposure to 17α-hydroxyprogesterone caproate impairs adult delayed reinforcement and reversal learning in male and female rats

Women with a history of unexplained miscarriage are frequently prescribed the synthetic progestin, 17 alpha-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.