Analysis of the molecular and neural mechanism involved in the placebo response by using mouse models for neuronal diseases.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07337
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Teikyo University (2020-2023); Tokushima Bunri University (2019)
• Principal Investigator: KIshimoto Yasushi 帝京大学, 薬学部, 教授 (90441592)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: プラセボ反応 / うつ病 / 疼痛 / 統合フレームワーク理論 / モルヒネ / 実験者効果

Outline of Final Research Achievements

By changing various conditions and systems, we were able to establish a system for evaluating the placebo response in mice, which was our initial goal. By evaluating the effects of pharmacological, genetic, and brain-destructive treatments on this system, we were able to elucidate the molecular mechanisms of the placebo response in the brain (mainly dopamine and endocannabinoid systems). However, cortical EEG analysis during the placebo response showed no changes, but the small number of cases may have been masked by individual differences in EEG. We analyzed three mouse models of neurological disease and were able to suggest the possibility of treatment by placebo effect in some strains. In addition, differences in experimental results by experimenter (experimenter effect) are under analysis at this time.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

マウスに対してプラセボおよびノセボ反応を再現性よく評価できる条件づけ系を確立した。拮抗薬、作動薬、合成酵素阻害剤などの効果を評価した結果、プラセボ反応におけるドパミン受容体やカンナビノイド受容体の重要性が明らかになった。さらに自閉症、統合症失調症、アルツハイマー病の３モデルマウスに対して本システムを適応し、野生型マウスに比べ、それぞれ特徴的な変異を呈することを明らかにした。本研究の学術的意義はシステムの確立自体に加え、プラセボ反応の分子的実態の一端を解明したことにある。今後、医療や治験においてプラセボ効果を積極的に活かす、もしくは減じる方法論を提示するものでありその社会的意義は大きいと考える。