Diazepam and exercise training combination synergistically reduces lipopolysaccharide-induced anxiety-like behavior and oxidative stress in the prefrontal cortex of mice

Anxiety-related disorders are among the most important risks for global health, especially in recent years due to the COVID-19 pandemic. Benzodiazepines like diazepam are generally used to treat anxiety disorders, but the overall outcome is not always satisfactory. This is why psychiatrists encourage patients with anxiety to change their lifestyle habits to decrease the risk of anxiety recurrence. However, the effect of diazepam and exercise in combination is unknown. This study aimed to investigate the effect of diazepam alone or in combination with swimming exercise on lipopolysaccharide (LPS)-induced anxiety-like behavior and oxidative stress in the hippocampus and prefrontal cortex of mice. Mice were exposed to diazepam and swimming exercise alone or in combination with each other and then received LPS. We assessed anxiety-like behavior using open field and light-dark box and measured oxidative markers including glutathione (GSH), malondialdehyde (MDA), and glutathione disulfide (GSSG) in the hippocampus and prefrontal cortex. The findings showed that LPS increased anxiety-related symptoms and oxidative stress by decreasing GSH and increasing MDA and GSSG levels in the prefrontal cortex but not in the hippocampus. Although diazepam alone did not reduce anxiety-like behavior and oxidative stress, it in combination with exercise significantly decreased anxiety-like behavior and oxidative stress in the prefrontal cortex of LPS-treated mice. This drug and exercise combination also displayed a more effective effect in comparison with exercise alone. Overall, this study suggests that diazepam in combination with swimming exercise has higher efficacy on anxiety-like behavior and oxidative stress than when they are used alone.