Effect of Vitamin D3 on Depressive Behaviors of Rats Exposed to Chronic Unpredictable Mild Stress

SIMPLE SUMMARY: Depression is a psychiatric disorder that represents a growing issue worldwide. This mental disorder is considered a mood disorder characterized by deep sadness and lethargy. A healthy diet is linked to enhanced mental health, whereas a bad diet is linked to an increased risk of depression and anxiety. Several studies have reported a positive association between vitamin D deficiency and depression. Therefore, we aimed to examine the effects of vitamin D3 (VD3) on a rat model of depression, which is induced by chronic unpredictable mild stress (CUMS). Behavioral tests were used to measure changes in depressive behaviors, as well as the levels of corticosterone and vitamin D in the blood. The groups that received doses of vitamin D produced better results than the group that did not receive any treatment in some behavioral tests. Vitamin D also had a protective role in preventing an increase of the corticosterone hormone, as well as an effective role in preventing a decrease in the level of vitamin D serum in the blood. The results of this research suggest that VD3 has a protective effect against anxiety and depression produced by CUMS in rats. ABSTRACT: Depression is a psychiatric disorder that negatively affects how a person feels, thinks, and acts. Several studies have reported a positive association between vitamin D (VD) deficiency and depression. Therefore, we aimed to examine the effects of intraperitoneal injection of VD3, fluoxetine (antidepressant), and a combination of VD3 + fluoxetine on a rat model of chronic unpredictable mild stress (CUMS). A total of 40 male Wistar rats (224–296 g) were divided into five groups (n = 8 each) as follows: (1) the control group, (2) the CUMS group, (3) the CUMS group that received vitamin D (10 μg/kg), (4) the CUMS group that received fluoxetine (5 mg/kg), and (5) the CUMS group that received both vitamin D (10 μg/kg) and fluoxetine (5 mg/kg). The CUMS model was produced by exposing rats to frequent social and physical stressors for 21 days. In addition, blood samples were collected to determine corticosterone and serum VD levels. Also, behavioral tests were conducted, including the sucrose preference test (SPT), the forced swimming test (FST), the tail suspension test (TST), the open field test (OFT), and the elevated plus maze test (EPM). Our results show that VD3 had effects similar to fluoxetine on the depressive behavior of the rats when measured by three behavioral tests, namely SPT, FST, and OFT (p < 0.001). Additionally, VD3 had a protective effect against depression similar to that of fluoxetine. Corticosterone levels were lower in the CUMS group that received vitamin D and the CUMS group that received both vitamin D and fluoxetine than in the CUMS group (p < 0.000). In conclusion, VD3 has a protective effect against anxiety and depressive behaviors produced by CUMS in rats.