Early post-stress administration of MR or GR antagonist in adolescent female rats restored anxiogenic-like behavior and modified the HPA axis response in the adulthood.

Several brain structures responsible for controlling stress responses reach maturity during adolescence. Therefore, acute or chronic stress in prepuberty may negatively affect stress responses as well as behavior in adulthood. The hypothalamus-pituitary-adrenal axis (HPA) is part of the stress system whose inhibitory control is regulated by glucocorticoids through mineralocorticoid (MR) and glucocorticoid (GR) receptors. In this study, we aimed to determine whether MR or GR blockade after stress in adolescence prevents changes in exploratory behavior and HPA axis control in adult female rats. Adolescent female rats (26 days old) were submitted to one or seven daily restraint sessions followed by administration of MR (spironolactone) or GR (RU-486) antagonists. At 60 days old, animals were evaluated in the elevated plus maze and at 61 days old rats were subjected to acute stress to evaluate the HPA response. The chronic restraint in the adolescence induced an anxiogenic effect in the adult animals that was reverted by either MR or GR antagonist. In the same way chronic stress reduced the HPA axis activity by blunted corticosterone (CORT) secretion and decreased the activation of Corticotropin Releasing Hormone (CRH) neurons in the paraventricular nucleus. The post-stress blocking of GR independently restored the CORT secretion without effect on central activation. The acute stress in the adolescence had minor enduring effects. We concluded that the use of RU-486 and spironolactone after stress in the early adolescence can improve behavioral changes induced by stress whereas RU-486 only showed effect on the HPA axis response in adulthood.

In utero and lactational exposure to fluoxetine delays puberty onset in female rats offspring.

Depression is one of the most prevalent disorders in the world and may occur during pregnancy and postpartum periods. Fluoxetine (FLX) has been widely prescribed for use during depression in pregnancy and lactation. This study aimed to investigate if in utero and lactational exposure to FLX could compromise reproductive parameters in female offspring. Wistar rats received, by daily gavage, FLX 5mg/kg or 0.3ml of water (control group) from the first gestational day until weaning (21 days). Assessments in the female offspring included: body weight, anogenital distance, vaginal opening, first estrus, estrous cycle, reproductive organs weight, uterine morphometric analyses, ovarian follicle and corpora lutea counting, estradiol plasmatic concentration, sexual behavior, maternal behavior and fertility test. Exposure to FLX delayed the puberty onset in female pups. The present study demonstrated that developmental exposure to FLX can deregulate the neuroendocrine hormonal control of female offspring during prepubertal and pubertal periods.

Effects of maternal exposure to the galactagogue Sulpiride on reproductive parameters in female rats.

The antipsychotic Sulpiride has been documented as an effective galactagogue that acts blocking dopamine receptors, increasing prolactin concentrations. However, this drug passes through the milk exposing neonates during postnatal development, which may result in functional and morphological alterations in adult life. Therefore, the aim of this study was to investigate whether maternal exposure to Sulpiride during lactation could impair reproductive development of female offspring. The dams were treated daily by gavage with Sulpiride doses of 2.5mg/Kg (SUL 2.5mg group) and 25mg/Kg (SUL 25mg group), or distilled water (Control group) throughout the lactation period. During early life, body weight, anogenital distance, and vaginal opening were analyzed on the female offspring. In adulthood, estrous cycle, sexual behavior, estrogen levels as well as the weight of the reproductive organs were evaluated. There were no differences regarding body weight, anogenital distance, puberty onset, frequency and duration of the estrous cycle and estradiol levels on female offspring. Nonetheless, there were changes in sexual behavior. There was an increase in the number of observations in reflex magnitude 0 (absence of lordosis) and reflex magnitude 2 as well as a reduction of reflex magnitude 3 in the rats of SUL 25mg group in relation to the Control group, suggesting a decrease in sexual receptivity of these animals. These results demonstrate that maternal exposure to Sulpiride can alter reproductive function in female offspring rats.