論文

査読有り 国際誌
2021年5月24日

Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonist-induced orofacial dyskinesia.

JCI insight
  • Koki Nagaoka
  • Takuya Nagashima
  • Nozomi Asaoka
  • Hiroki Yamamoto
  • Chihiro Toda
  • Gen Kayanuma
  • Soni Siswanto
  • Yasuhiro Funahashi
  • Keisuke Kuroda
  • Kozo Kaibuchi
  • Yasuo Mori
  • Kazuki Nagayasu
  • Hisashi Shirakawa
  • Shuji Kaneko
  • 全て表示

6
10
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1172/jci.insight.145632

Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the US Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevented the dyskinesia induced by dopamine D2 receptor antagonists. In vivo experiments further showed that a 21-day treatment with haloperidol increased the number of vacuous chewing movements (VCMs) in rats, an effect that was inhibited by oral acetaminophen treatment or intracerebroventricular injection of N-(4-hydroxyphenyl)-arachidonylamide (AM404), an acetaminophen metabolite that acts as an activator of the transient receptor potential vanilloid 1 (TRPV1). In mice, haloperidol-induced VCMs were also mitigated by treatment with AM404 applied to the dorsal striatum, an effect not seen in TRPV1-deficient mice. Acetaminophen prevented the haloperidol-induced decrease in the number of c-Fos+preproenkephalin+ striatal neurons in wild-type mice but not in TRPV1-deficient mice. Finally, chemogenetic stimulation of indirect pathway medium spiny neurons in the dorsal striatum decreased haloperidol-induced VCMs. These results suggest that acetaminophen activates the indirect pathway neurons by activating TRPV1 channels via AM404.

リンク情報
DOI
https://doi.org/10.1172/jci.insight.145632
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33857021
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262333
ID情報
  • DOI : 10.1172/jci.insight.145632
  • PubMed ID : 33857021
  • PubMed Central 記事ID : PMC8262333

エクスポート
BibTeX RIS