Repeated, high-dose dextromethorphan treatment decreases neurogenesis and results in depression-like behavior in rats.
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.
ST 507, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China.
Kai Ting
KT
Po
Andrew Man-Hong
AM
Siu
Benson Wui-Man
BW
Lau
Jackie Ngai-Man
JN
Chan
Kwok-Fai
KF
So
Chetwyn C H
CC
Chan
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003712:Dendrites / Q000378:metabolism; D003863:Depression / Q000139:chemically induced* / Q000473:pathology*; D003915:Dextromethorphan / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology*; D007398:Interpersonal Relations; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming / Q000523:psychology; D013997:Time Factors
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D003915:Dextromethorphan; D001973:Bromodeoxyuridine