Roles of adrenaline receptor subtypes in regulation of cholinergic activity in nucleus accumbens

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09777
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Nihon University
• Principal Investigator: AONO Yuri 日本大学, 松戸歯学部, 専修研究員 (50508497)
• Co-Investigator(Kenkyū-buntansha): 三枝 禎 日本大学, 松戸歯学部, 教授 (50277456)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 脳微小透析法 / ACh / 側坐核

Outline of Final Research Achievements

The nucleus accumbens (NAc) is a major terminal area of mesolimbic dopaminergic system. Cholinergic neurons in the NAc contain GABAA and GABAB receptors (-Rs) that are thought to inhibit neural activity. We analyzed the roles of GABAA- and GABAB-Rs in regulating accumbal acetylcholine (ACh) efflux of freely moving rats using in vivo microdialysis. The effects of GABA-R ligands on the accumbal dopamine efflux were also analyzed since accumbal cholinergic and dopaminergic neurons could mutually interact. The NAc contains cholinergic interneurons that might receive inputs from noradrenergic projections and alpha-R ligands modulate accumbal cholinergic activity-dependent locomotion of rats. Therefore, in order to examine the involvement of α2-Rs in the regulation of accumbal cholinergic neural activity, we further investigated the effects of the α2-R agonist UK 14304 and the α2-R antagonist RX 821002 on the accumbal ACh efflux.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

側坐核では，DA神経とACh神経の間で密接な機能的相互作用が起こることが知られている。本研究は，側坐核において両神経を抑制的に制御するGABAAおよびGABAB受容体がDA神経活動には影響を与えずにACh神経活動を抑制できることを報告できた点が意義深い。また本計画では，NA神経が側坐核のα2受容体を介してACh神経活動を抑制的に制御することを示す神経薬理学的知見を得ることができた。このことはNA神経による側坐核のACh神経活動の調節機構のほか，抗うつ薬をはじめとする脳内のNA神経を作用点とする薬物のACh神経への作用メカニズムの解明のヒントとなるものであった。