Vagus nerve-dependent effects of fluoxetine on anxiety- and depression-like behaviors in mice

The vagus nerve is a major pathway in the body that is responsible for regulating the activity of the parasympathetic nervous system, which plays an important role in mood disorders including anxiety and depression. Fluoxetine, also known as Prozac, is widely used to treat depression. Nevertheless, there are few studies on the vagus nerve-mediated action of fluoxetine. In this study, we aimed to investigate the vagus nerve-dependent actions of fluoxetine in mice with restraint stress-induced or antibiotics-induced anxiety- and depression-like behaviors. Compared to sham operation, vagotomy alone did not exhibit significant effects on behavioral changes and serotonin-related biomarkers in mice not exposed to stress, antibiotics, or fluoxetine. Oral administration of fluoxetine significantly alleviated anxiety- and depression-like behaviors. However, celiac vagotomy significantly attenuated the anti-depressive effects of fluoxetine. The vagotomy also inhibited the effect of fluoxetine to attenuate restraint stress- or cefaclor-induced reduction in serotonin levels and Htr1a mRNA expression in the hippocampus. These findings suggest that the vagus nerve may regulate the efficacy of fluoxetine for depression.