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

• 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
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2016.10.001

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.