Different Effects of Fluoxetine and Paroxetine Combined with Vitamin D3 in Ovariectomized Rats Exposed to Unpredictable Stress

Abstract

Background: Vitamin D3 (VD3) is involved in the pathophysiological mechanisms of affective-related disorders and controls the functional activity of various hormonal systems. The complex interaction between estrogen and VD3 creates a neurobiological basis for their participation in similar behavioral disorders. Objectives: This study aimed to evaluate whether VD3 (5.0 mg/kg, s.c.) facilitates the antidepressant-like action of fluoxetine (10.0 mg/kg, i.p.) or paroxetine (10.0 mg/kg, i.p.) by enhancing the antidepressant-like activity of these drugs in adult long-term Ovariectomized (OVX) rats subjected to Chronic Unpredictable Mild Stress (CUMS) protocol for 6 weeks. Methods: Sucrose Preference (SPT) and Forced Swim (FST) tests were performed to evaluate the anhedonia state and depressive symptoms, respectively. The Open-Field Test (OFT) was carried out to measure locomotor activity as well as grooming behavior produced by CUMS in long-term OVX rats. Corticosterone (CS)/estradiol (E2) in the serum was tested by rat ELISA kits. NF-kB, 5-HT/5-HIIA, and pro-inflammatory cytokine levels in the hippocampus were also examined by rat ELISA kits. Results: The results of this study suggest that combined treatment with fluoxetine (10.0 mg/kg, i.p.) or paroxetine (10.0 mg/kg, i.p.) along with VD3 (5.0 mg/kg, s.c.) produces distinct effects on the depression-like behavior in long-term OVX/CUMS rats. Co-administration of fluoxetine (10.0 mg/kg, i.p.) with VD3 did not facilitate the antidepressant-like effects of fluoxetine in the long-term OVX rats with CUMS. On the other hand, co-treatment with paroxetine with VD3 resulted in faster and marked antianhedonic- and antidepressant-like effects in long-term OVX rats with CUMS as compared to treatment with paroxetine alone. The co-administration of paroxetine and VD3 attenuates stress-induced modifications of CS/E2 levels in the serum, as well as- proinflammatory cytokine/NF-kB/5-HT levels in the hippocampus of long-term OVX rats exposed to CUMS. Conclusion: Supplementation of VD3 (5.0 mg/kg, s.c.)to paroxetine (10.0 mg/kg, i.p.) facilitates antianhedonic- and antidepressant-like effects of paroxetine in adult long-term OVX rats exposed to CUMS.