Abstract
Major depressive disorder is a prevalent and debilitating psychiatric illness that produces significant disability. Clinical data suggest that the pathophysiology of depression is due, in part, to a dysregulation of inflammation and glutamate levels in the brain. The systemic administration of lipopolysaccharide (LPS) has been shown to induce depressive-like behaviors in mice. Dapagliflozin (DPG), a sodium-glucose cotransporter-2 inhibitor (SGLT2i), used to treat type 2 diabetes, has been reported to produce neuroprotective effects in various animal models. This study aimed to determine the efficacy of DPG (0.5 mg/kg) to decrease LPS-induced depressive-like behaviors in mice. Thirty-six male mice were divided into four groups (n = 9): Saline (normal saline, 1 mL/kg, i.p., for 14 days), LPS (saline for 7 days followed by 1 mg/kg of LPS, i.p.), DPG (0.5 mg/kg, oral gavage for 14 days), and LPS and DPG (DPG alone for 7 days, followed by LPS and DPG for another 7 days). The forced swim (FST) and tail suspension tests (TST), putative animal models of depression, were conducted at the end of the study. After euthanization, brain tissues and blood samples were collected. The expression of glutamate transporter 1 (GLT-1), solute carrier family 7-member 11 (SLC7A11), and nuclear factor kappa β (NF-κB) mRNA was determined using q-PCR. LPS induced depressive-like behavior and significantly increased mRNA levels of GLT-1, SLC7A11, and NF-κB. DPG alone also affected baseline performance in the TST. Furthermore, DPG significantly decreased the LPS-induced changes, suggesting that it may alleviate LPS-induced depressive behaviors by modulating glutamate homeostasis and inflammatory pathways.