The relation of ambient temperature and Serotonin syndrome by 25B-NBOMe

• Project/Area Number: 16K09215
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Nakamura Mami 京都府立医科大学, 医学(系)研究科(研究院), 助教 (70753763)
• Co-Investigator(Kenkyū-buntansha): 新谷 香 (石田香) 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50345047)
• Research Collaborator: Tojo Misa ; Ikegaya Hiroshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 末梢セロトニン / 環境温度 / 薬剤性高体温 / 5－HT2A受容体 / 5-HT2A受容体 / セロトニン / 体温調節 / 高体温 / 生理学 / 薬学 / 神経科学

Outline of Final Research Achievements

We investigated changes in body temperature of rats after administration of 25B-NBOMe, a selective agonist of 5-HT2A receptor, under general or high ambient temperature. Administration of 25B-NBOMe induced hyperthermia only at a high ambient temperature.Peripheral vasoconstriction was observed in the early phase, and thermogenesis in brown adipose tissue (BAT) and decrease of plasma serotonin levels were observed in the late phase of hyperthermia. Peripheral administration of serotonin or 5-HT2A blocker which do not pass the blood-brain-barrier, and selective destruction of central noradrenaline or serotonin neurons indicated a thermoregulation pathway independent from central neural pathways. These results suggest that peripheral serotonin plays an important role in thermoregulation.

Academic Significance and Societal Importance of the Research Achievements

環境温度に依存した体温調節メカニズムの解明は、薬剤性高体温のみならず、高体温を起こす様々な疾患の病態解明や治療に不可欠である。その中で、これまで研究されてきた中枢性の体温調節機構ではなく、末梢に独立した体温調節機構が存在し末梢セロトニンが関与すると示唆されたことは、今後の生理学研究に新しい視点を加えるものと考える。

Research Products

• [Journal Article] 5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperatures (2018)
  • Author(s): Mami Nakamura, Kaori Shintani-Ishida, Hirosi Ikegaya
  • Journal Title: The Journal of Pharmacology and Experimental Therapeutics Volume: 367 Issue: 2 Pages: 356-362
  • DOI: 10.1124/jpet.118.250217
  • Peer Reviewed
• [Journal Article] Experimental Study on the Postmortem Redistribution of the Substituted Phenethylamine, 25B-NBOMe (2017)
  • Author(s): Shintani-Ishida Kaori、Saka Kanju、Nakamura Mami、Yoshida Ken-ichi、Ikegaya Hiroshi
  • Journal Title: Journal of Forensic Sciences Volume: 63 Issue: 2 Pages: 588-591
  • DOI: 10.1111/1556-4029.13583
  • Peer Reviewed
• [Presentation] 高温環境下における薬剤性高体温への末梢セロトニンの関与 (2017)
  • Author(s): 中村磨美、新谷香、東條美紗、市岡宏顕、坪井創、高相真鈴、池谷博
  • Organizer: 第101回日本法医学全国学術集会
• [Presentation] フェネチルアミン系化合物25B-NBOMeの死後再分布に関する実験的検討 (2016)
  • Author(s): 新谷 香、坂 幹樹、吉田 謙一、池谷 博
  • Organizer: 日本法中毒学会第35年会
  • Place of Presentation: 大阪産業創造館（大阪市）
  • Year and Date: 2016-07-01
• [Presentation] 25B-NBOMeにより刺激された5-HT2A受容体は環境温度依存性に高体温を引き起こす (2016)
  • Author(s): 中村 磨美、新谷 香、東條 美紗、井戸田 望、池谷 博
  • Organizer: 第100回日本法医学全国学術集会
  • Place of Presentation: きゅりあん（東京都品川区）
  • Year and Date: 2016-06-16