Sex-specific effects of early neonatal progesterone treatment on dopamine and serotonin metabolism in rat striatum and frontal cortex

AimsThe early neonatal period is critical for the development of the rodent brain. Neurosteroid levels in the brain decline from the late gestation to the neonatal period. Previous studies indicate effects of neurosteroid treatment during the neonatal period on the development of the dopaminergic system. In this study, we investigated the sex-specific effects of neonatal treatment with the neurosteroid progesterone on monoamine metabolism. Separately, we examined the contribution of pre-pubertal castration on the effect of neonatal treatment of pregnenolone (a neurosteroid precursor).Main methodsProgesterone (Experiment 1) or pregnenolone (Experiment 2) treatments in Sprague-Dawley rats were performed from postnatal days 3 through 7. Castration in experiment 2 was performed in male rats at postnatal day 21. We measured the brain tissue contents of dopamine, serotonin (5-HT), and their metabolites in rats at age 10 weeks.Key findingsResults showed that neonatal progesterone treatment altered striatal 5-hydroxy-3-indolacetic acid/5-HT ratios in males and females in opposite directions, in addition to dopaminergic effects. The treatment also influenced dopamine and 5-HT metabolism without sex-specificity in the frontal cortex. In addition, there was no significant difference in striatal monoamine metabolism between sham-operated, castrated and castrated pregnenolone-treated group.SignificanceThe present result indicates a sex-specific influence of progesterone during the early neonatal period on the development of the serotonergic system, depending on brain region in addition to of the dopaminergic system.