Repeated, high-dose dextromethorphan treatment decreases neurogenesis and results in depression-like behavior in rats
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Abuse of cough mixture is increasingly prevalent worldwide. Clinical studies showed that chronic consumption of cough mixture at high dosages may lead to psychiatric symptoms, especially affective disturbances, with the underlying mechanisms remain elusive. The present study aims at exploring the effect of repeated, high-dose dextromethorphan (DXM, a common active component of cough mixture) treatment on adult hippocampal neurogenesis, which is associated with pathophysiology of mood disturbances. After treatment with a high-dose of DXM (40 mg/kg/day) for 2 weeks, Sprague–Dawley rats showed increased depression-like behavior when compared to the control animals. Neurogenesis in the hippocampus was suppressed by DXM treatment, which was indicated by decreases 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. These findings suggest that DXM induces depression- and anxiety-like behavior and suppresses neurogenesis in rats. The current experimental paradigm may serve as an animal model for study on affective effect of cough mixture abuse, rehabilitation treatment options for abusers and the related neurological mechanisms.
KeywordsNeurogenesis Dextromethorphan Depression-like behavior Anxiety-like behavior Drug abuse
The current study is supported by the departmental general research grant, Department of Rehabilitation Science, The Hong Kong Polytechnic University. The authors would like to thank Dr Guo Xia, Mr Ani Lee and Edward Leung for their technical assistance, and Dr. Guo’s comments on the project design.
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