Elucidation of the mechanism of abnormal motivation in behavioral addiction by 5-HT.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15290
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kanazawa University
• Principal Investigator: Naoya Nishitani 金沢大学, 薬学系, 助教 (30824792)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 行動嗜癖 / ドパミン / 側坐核 / 5-HT / オペラント / ランニングホイール

Outline of Final Research Achievements

The present study used an operant task with a wheel running reward. Fiber　photometry recordings of dopamine release and neural activity in the nucleus accumbens (NAc) during the task revealed that DA release increased before motivational behavior and after reward acquisition, and neural activity decreased around motivational behavior and increased after reward acquisition. Inhibition of 5-HT2A and 2C receptors decreased motivation for wheel running but did not affect changes in DA release in the NAc. In addition, we created a mouse model of behavioral addiction based on clinical diagnostic criteria for addiction and found that approximately 35% of the mice were classified as behavioral addiction model mice. Furthermore, it is suggested that activation of cannabinoid CB1 and 5-HT2A receptors may be involved in the formation of behavioral addiction pathology model mice.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

インターネットやゲーム、ギャンブル等に病的にのめり込む行動嗜癖は社会問題となっているが、実験動物を用いた病態メカニズムの研究はほとんど存在しない。本研究では、行動嗜癖の病態メカニズムにおいて、側坐核でのDA遊離変化と神経活動変化が重要であることを解明した。また、5-HT2Aおよび2C受容体の関与も示唆されたが、これはDA遊離へ影響するのではなく、それ以外のメカニズムで作用することが示唆された。最後に、臨床に即した行動嗜癖病態モデルマウスの作製に成功し、病態形成へのCB1および5-HT2A受容体の関与が示唆された。これらの受容体を標的とすることで行動嗜癖の治療法、治療薬開発に繋がると期待される。