Effects of ketamine on depressive-like behaviors and prefrontal neuronal circuit

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K09341
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Hirosaki University
• Principal Investigator: Nikaido Yoshikazu 弘前大学, 医学研究科, 講師 (50613478)
• Co-Investigator(Kenkyū-buntansha): 廣田 和美 弘前大学, 医学研究科, 教授 (20238413) ; 櫛方 哲也 弘前大学, 医学研究科, 准教授 (80250603)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: うつ病 / ケタミン / Arc / In vivo マルチユニット記録 / In vivo Ca2+イメージング

Outline of Final Research Achievements

In this study, we investigated the neuronal activity in the medial prefrontal cortex (mPFC) and the effect of low-dose ketamine on the mPFC neurons using chronic social defeat stress (CSDS) model mice. CSDS model mice showed depressive-like behaviors and decreased number of Arc-positive cells in the mPFC. Low-dose ketamine inhibited these behavioral and neuronal alternations of CSDS model mice. Furthermore, in vivo multi-unit recordings and Ca2+ imaging demonstrated that Arc-expressing excitatory neurons in the mPFC might play essential roles in the anti-depressant effects of low-dose ketamine.

Free Research Field

行動神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究課題は内側前頭前野においてうつ病の病態発現に関与する可能性がある神経細胞群の種類を推定し、抗うつ作用の臨床応用が期待される低用量ケタミンが内側前頭前野の神経活動に与える影響を明らかにした。これらの成果はうつ病病態が発現する機序の解明に加え、ケタミンを用いたうつ病新規治療戦略の基礎的な理解、安全な運用に向けた今後の研究開発に繋がる有益な情報基盤になる。