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

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 SEPT, TPH, and 5-HT1A 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.

Automated summary

Overexposure to glucocorticoids during gestation can lead to long-term mental disorders, and this study investigates the effects of late gestational administration of dexamethasone and vitamin D on depressive-like behavior in adult female rats. The results show that prenatal vitamin D and dexamethasone can affect sucrose preference, and prenatal vitamin D has an antidepressant-like effect in rats overexposed to dexamethasone, although this effect is blunted at a later stage. The protein content of certain receptors in the dorsal raphe nucleus is also affected by prenatal dexamethasone exposure. The study concludes that prenatal overexposure to dexamethasone can modify the effects of prenatal vitamin D on depressive behavior in a time-dependent manner, and these effects are not related to alterations in the serotonergic system or glucocorticoid receptor expression in the dorsal raphe nucleus.