Antidepressant-like activity of gestational administration of vitamin D is suppressed by prenatal overexposure to dexamethasone in female Wistar rats

Abstract

Overexposure to glucocorticoids during gestation can lead to long-term mental disorders. Given the higher prevalence of depression in females, we investigated whether late gestational administration of dexamethasone could generate a depressive-like phenotype in the adult female offspring and if vitamin D could have a neuroprotective effect in this context. Pregnant rats received vitamin D (VitD, 500 IU/day) or vehicle (CTL) during gestation. Other pregnant rats received dexamethasone (Dex 0.1 mg/kg/ - 14th to the 19th gestational day) or dexamethasone + vitamin D (DexVitD). The offspring were tested for anhedonia (sucrose preference) and depressive-like behavior (forced swimming test) at postnatal months (PNM) 3, 6 and 12. Components of the serotonergic system, as well as glucocorticoids' receptors, were evaluated in the dorsal raphe nucleus at PNM 6 and 12. Prenatal vitamin D and dexamethasone increased sucrose preference at PNM 12. Prenatal vitamin D had an antidepressant-like effect at PNM 3 in rats overexposed to dexamethasone. However, at PNM 12, this effect was blunted in the DexVitD group. Prenatal dexamethasone reduced the protein content of SERT, TPH, and 5-HT_1A receptors in the dorsal raphe nucleus at 6 but not at 12 PNM. The glucocorticoids' receptors expression was similar in all groups. We concluded that prenatal overexposure to dexamethasone does not change emotional behaviors in females, but it blunts the antidepressant-like effect of gestational vitamin D in an age-dependent manner. The antidepressant-like activity of vitamin D in the offspring was not related either to alterations of the serotonergic system or the glucocorticoids' receptors expression in the dorsal raphe nucleus.

Keywords: Anhedonia; Depression; Dorsal raphe nucleus; Fetal programming; Glucocorticoids.