Lycopene ameliorates PTSD-like behaviors in mice and rebalances the neuroinflammatory response and oxidative stress in the brain

Posttraumatic stress disorder (PTSD) is a mental disorder that can translate into severe economic problems. Lycopene is an aliphatic hydrocarbon carotenoid extracted from plants, including papayas, tomatoes, and water melons. Previous studies have shown that lycopene can produce antidepressant-like effects in rodent models of depression. However, little is known about its anti-PTSD-like effect. This was addressed in the present study by using the single prolonged stress (SPS) protocol to induce PTSD-like behavioral deficits in mice. Our results showed that 12 days of lycopene treatment at the dose of 10 and 20 mg/kg, but not at 5 mg/kg, ameliorated the PTSD-like phenotype induced by SPS, including the increase in freezing time in contextual fear paradigm, the decrease in time and entries in open arms in elevated plus maze test, and the decrease in distance and time in the central area of the open field test, without affecting the mouse locomotor activity. Mechanistic studies revealed that lycopene treatment (20 mg/kg, 12 days) could suppress the SPS-induced increase in levels of interleukin-6 (IL-6), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), and nitrite in the hippocampus and prefrontal cortex in mice, as well as the increased markers that indicate high levels of oxido-nitrosative stress in the hippocampus and prefrontal cortex in SPS mice. Lycopene treatment (20 mg/kg, 12 days) also suppressed the SPS-induced decrease in brain derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex in mice. Overall, the anti-PTSD-like effect of lycopene may be associated with its anti-neuroinflammation and anti-oxidative stress activities.