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

• Nagaoka, Koki

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Nagashima, Takuya

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Asaoka, Nozomi

  Department of Pharmacology, Kyoto Prefectural University of Medicine

• Yamamoto, Hiroki

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Toda, Chihiro

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Kayanuma, Gen

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Siswanto, Soni

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Funahashi, Yasuhiro

  Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University

• Kuroda, Keisuke

  Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University

• Kaibuchi, Kozo

  Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University

• Mori, Yasuo

  Deaprtment of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University

• Nagayasu, Kazuki

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Shirakawa, Hisashi

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

• Kaneko, Shuji

  Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University

Bibliographic Information

Other Title

• Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonist–induced orofacial dyskinesia

Abstract

Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the U.S. Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevents 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, but not 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.

Journal

• JCI Insight

  JCI Insight 6 (10), e145632-, 2021-05

  American Society for Clinical Investigation

Keywords

• General Medicine

Details

• CRID: 1050851165478874880
• NII Article ID: 120007038817
• DOI: 10.1172/jci.insight.145632
• HANDLE: 2433/262976
• ISSN: 23793708
• Web Site: https://insight.jci.org/articles/view/145632/files/pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN