Experimental Brain Research

, Volume 233, Issue 7, pp 2205–2214 | Cite as

Repeated, high-dose dextromethorphan treatment decreases neurogenesis and results in depression-like behavior in rats

  • Kai Ting Po
  • Andrew Man-Hong Siu
  • Benson Wui-Man LauEmail author
  • Jackie Ngai-Man Chan
  • Kwok-Fai So
  • Chetwyn C. H. Chan
Research Article


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.


Neurogenesis 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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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Kai Ting Po
    • 1
  • Andrew Man-Hong Siu
    • 1
  • Benson Wui-Man Lau
    • 1
    Email author
  • Jackie Ngai-Man Chan
    • 1
  • Kwok-Fai So
    • 2
    • 3
    • 4
  • Chetwyn C. H. Chan
    • 1
  1. 1.ST 507, Department of Rehabilitation SciencesThe Hong Kong Polytechnic UniversityHong KongChina
  2. 2.The State Key Laboratory of Brain and Cognitive SciencesThe University of Hong KongPokfulamHong Kong
  3. 3.Department of OphthalmologyThe University of Hong KongPokfulamHong Kong
  4. 4.GMH Institute of CNS Regeneration, and Guangdong Medical Key Laboratory of Brain Function and DiseasesJinan UniversityGuangzhouChina

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