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

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....

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmacological sciences 2016-10, Vol.132 (2), p.166-170
Main Authors: Tran, Hai-Quyen, Chung, Yoon Hee, Shin, Eun-Joo, Kim, Won Ki, Lee, Jae-Chul, Jeong, Ji Hoon, Wie, Myung Bok, Jang, Choon-Gon, Yamada, Kiyofumi, Nabeshima, Toshitaka, Kim, Hyoung-Chun
Format: Article
Language:English
Subjects:
Administration route
Animals
Antitussive Agents - administration & dosage
Antitussive Agents - toxicity
Cytosol - drug effects
Cytosol - pathology
Cytosol - ultrastructure
Dextromethorphan - administration & dosage
Dextromethorphan - toxicity
High-dose dextromethorphan
Hippocampus - drug effects
Hippocampus - pathology
Hippocampus - ultrastructure
Injections, Intraperitoneal
Mitochondria - drug effects
Mitochondria - pathology
Mitochondria - ultrastructure
Myelin Sheath - pathology
Myelin Sheath - ultrastructure
Myelinoid bodies with mitochondrial dysfunction
Rats
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1347-8613
1347-8648
DOI:10.1016/j.jphs.2016.10.001