Regulation of depression-like behaviour and neurogenesis by dextromethorphan

Background and purpose: Chronic consumption of cough mixture at high dosages leads to psychiatric symptoms, especially emotional disturbances, with the underlying mechanism remains elusive. This study aims to assess the effect of chronic, high-dose dextromethorphan (DXM) administration on adult hippocampal neurogenesis (i.e. production of new neurons), which is associated with pathophysiology of mood disorders. Methods: Sprague-Dawley rats were divided into control (vehicle injection) and DXM-treatment groups (40 mg/ kg, intraperitoneal injection). After treatment for 2 weeks, the animals were tested for depression-like behaviour, followed by euthanasia and neurogenesis assays. Results: After treatment with a high-dose DXM, the rats showed increased depression-like behaviour in forced swimming test. Neurogenesis in the hippocampus was suppressed by DXM treatment, which was indicated by a decrease in number of proliferative cells and doublecortin (an immature neuron marker) positive new neurons. Furthermore, the dendritic complexity of the immature neurons was suppressed by DXM treatment. Conclusion: Chronic DXM treatment induced depression-like behaviour and suppressed neurogenesis in the hippocampus. This animal model may be used for studying the affective effect of cough medicine abuse, rehabilitation treatment options for abusers, and the related neurological mechanisms.