The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae

Author:

Kawahara Genri,Maeda Hideyuki,Kikura-Hanajiri Ruri,Yoshida Ken-ichi,Hayashi Yukiko K.

Abstract

Abstract N-Benzyl-substituted 2C class phenethylamines (NBOMes) are psychoactive designer drugs, with strong hallucinogenic and stimulant effects, even at low doses. The designer drug, 2-(4-bromo-2, 5-dimethoxyphenyl)-N-(2-methoxybenzyl) ethanamine (25B-NBOMe) is considered to be one of the most potent agonists of the serotonin-2A (5-HT2A) receptor. Recently, we reported the first lethal case of 25B-NBOMe intoxication with severe rhabdomyolysis, concluded by clinical, pathological and toxicological analyses. There are currently no good animal models that closely recapitulate serotonin receptor-dependent rhabdomyolysis. In the present study, we created animal models of rhabdomyolysis using zebrafish larvae to study the pathomechanism of rhabdomyolysis, and demonstrated that 25B-NBOMe can simulate lethal rhabdomyolysis in this animal. Treatment of the larvae with 25B-NBOMe decreased their survival rate, locomotion, altered birefringence of the skeletal muscle and immunostainings for dystroglycan (a myoseptal protein) and myosin heavy chain (a myofibril protein), which were consistent with rhabdomyolysis. This 25B-NBOMe-induced rhabdomyolysis was inhibited by the 5-HT2A receptor antagonists ritanserin and aripirazole, but not by the 5-HT1A + 5-HT1B receptor antagonist propranolol and the 5-HT3 receptor antagonist granisetron, indicating 5-HT2A-dependent rhabdomyolysis. The 25B-NBOMe-treated zebrafish is, therefore, a highly useful model of rhabdomyolysis for studying the pathomechanism of rhabdomyolysis as well as for therapeutic drug screening.

Funder

A Grant-in-Aid for Challenging Exploratory Research

The MEXT-Supported Program for the Strategic Research Foundation at Private Universities

Research on Rare and intractable Diseases, Health and Labor Science Research Grants

The National Center of Neurology and Psychiatry Intramural Research Grant for Neurological and Psychiatric Disorders

Grant-in-Aid for Scientific Research

Publisher

Springer Science and Business Media LLC

Subject

Biochemistry (medical),Toxicology,Pathology and Forensic Medicine

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