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 LAU, Jackie Ngai-Man CHAN, Kwok-Fai SO, Che Hin Chetwyn CHAN

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10 Citations (Scopus)

Abstract

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. Copyright © 2015 Springer-Verlag Berlin Heidelberg.
Original languageEnglish
Pages (from-to)2205-2214
JournalExperimental Brain Research
Volume233
Early online dateMay 2015
DOIs
Publication statusPublished - Jul 2015

Citation

Po, K. T., Siu, A. M.-H., Lau, B. W.-M., Chan, J. N.-M., So, K.-F., & Chan, C. C. H. (2015). Repeated, high-dose dextromethorphan treatment decreases neurogenesis and results in depression-like behavior in rats. Experimental Brain Research, 233, 2205-2214. doi: 10.1007/s00221-015-4290-0

Keywords

  • Neurogenesis
  • Dextromethorphan
  • Depression-like behavior
  • Anxiety-like behavior
  • Drug abuse

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