High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats

Hai Quyen Tran, Yoon Hee Chung, Eun Joo Shin, Won-Ki Kim, Jae Chul Lee, Ji Hoon Jeong, Myung Bok Wie, Choon Gon Jang, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung Chun Kim

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Abstract

Dextromethorphan (DM) administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg) to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed.

Original languageEnglish
Pages (from-to)166-170
Number of pages5
JournalJournal of Pharmacological Sciences
Volume132
Issue number2
DOIs
Publication statusPublished - 2016 Oct 1

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Keywords

  • Administration route
  • High-dose dextromethorphan
  • Myelinoid bodies with mitochondrial dysfunction

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Tran, H. Q., Chung, Y. H., Shin, E. J., Kim, W-K., Lee, J. C., Jeong, J. H., Wie, M. B., Jang, C. G., Yamada, K., Nabeshima, T., & Kim, H. C. (2016). High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats. Journal of Pharmacological Sciences, 132(2), 166-170. https://doi.org/10.1016/j.jphs.2016.10.001