Taurine and Bupropion Co-Administration in Depression: A CUMS-Based Preclinical Study

Major depressive disorder (MDD) is a debilitating psychiatric illness marked by persistent anhedonia, cognitive deficits, and neurochemical dysregulation. Conventional antidepressants often exhibit delayed onset, limited efficacy, and adverse side effects, emphasizing the need for novel therapeutic strategies. Taurine, a neuroprotective GABAergic modulator, and Bupropion, a norepinephrine-dopamine reuptake inhibitor (NDRI), possess distinct yet complementary mechanisms that may synergistically enhance antidepressant efficacy. Additionally, Bupropion exerts anti-inflammatory effects by reducing interleukin-6 (IL-6), a pro-inflammatory cytokine implicated in depression. This study evaluated the individual and combined antidepressant effects of Taurine and Bupropion in a chronic unpredictable mild stress (CUMS)-induced mouse model of depression. Male Swiss albino mice were exposed to CUMS for six weeks, followed by treatment with Taurine (25 mg/kg), Bupropion (10 mg/kg), or their combinations (Taurine 12.5 mg/kg + Bupropion 5 mg/kg; Taurine 25 mg/kg + Bupropion 10 mg/kg). Behavioral outcomes were assessed using the Forced Swim Test (FST), Tail Suspension Test (TST), Open Field Test (OFT), and locomotor activity measurement. Neurochemical analysis included gamma-aminobutyric acid (GABA), norepinephrine (NE), dopamine (DA), and IL-6 levels. Taurine monotherapy improved locomotion, exploratory behavior, and GABAergic tone, while Bupropion elevated NE and DA and reduced IL-6, reflecting neurochemical and anti-inflammatory benefits. The high-dose combination (Taurine 25 mg/kg + Bupropion 10 mg/kg) produced the most robust antidepressant-like effects, enhancing GABA, NE, and DA while markedly suppressing IL-6. These findings highlight the synergistic antidepressant potential of Taurine and Bupropion in restoring neurotransmitter balance and reducing neuroinflammation.