Lycopene attenuates dexamethasone-induced depression-like behavior and restores neuro-immune-metabolic balance in rats

Chronic glucocorticoid therapy, while essential for many conditions, frequently causes severe neuropsychiatric side effects, including depression-like behaviors, alongside systemic immunosuppression and metabolic dysfunction. This complex interplay of central neurotoxicity and peripheral immune dysregulation poses a significant therapeutic challenge, highlighting the need for multi-target interventions that can address these interconnected pathways. This study explores a prophylactic strategy.

Researchers investigated lycopene as a prophylactic against dexamethasone-induced perturbations in 32 adult male Sprague-Dawley rats (n=8 per group). Groups included normal control, dexamethasone (2 mg/kg/day intraperitoneal), lycopene (10 mg/kg/day orally), and a combination. Treatments were administered daily for 21 days. Behavioral assessments included forced swim test and tail suspension test. Neurochemical markers (BDNF, GABA, AChE activity), neurotransmitters (serotonin, dopamine), oxidative stress markers (MDA, NO, GSH, SOD, catalase), inflammatory cytokines (TNF-alpha, IL-6), and caspase-3 were quantified in brain tissues. Serum markers like fasting blood glucose, insulin, CD4, CD8, and CBC were also analyzed.

Dexamethasone administration significantly (p < 0.05) increased immobility time in both forced swim test and tail suspension test, indicating pronounced depression-like behavior. This was accompanied by a depletion of brain serotonin and dopamine levels, alongside elevated oxidative stress markers and inflammatory cytokines in both brain and serum. Dexamethasone also induced leukopenia and disrupted CD4/CD8 ratios, signifying immune dysfunction. Lycopene co-treatment effectively reversed these detrimental effects. > Lycopene restored neurotransmitter homeostasis, attenuated oxidative-inflammatory cascades, and normalized immune cell populations, demonstrating a comprehensive protective effect against dexamethasone-induced neuro-immune-metabolic dysregulation. The co-treatment also reversed behavioral despair and normalized serum markers related to metabolic and immune function, indicating a broad prophylactic efficacy.