Roles of delta- and mu-opioid receptors in the nucleus accumens in the control of accumbal GABAergic neural activity

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K24132
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Nihon University
• Principal Investigator: WATANABE Yuriko 日本大学, 松戸歯学部, 専修医 (90849340)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: GABA / オピオイド受容体 / 麻薬性鎮痛薬 / ラット

Outline of Final Research Achievements

The nucleus accumbens (NAc) is a major terminal area of mesolimbic dopaminergic neurons that originate in the ventral tegmental area. The NAc contains GABAergic neurons that interact with dopaminergic neurons. We analyzed the role of the GABA transporter (GAT) in regulation of basal extracellular GABA levels in the NAc of freely moving rats using in vivo microdialysis. The GAT1 inhibitor NNC711 and the GAT3 inhibitor (S)-SNAP-5114 were each administered directly into the NAc through the microdialysis probe. The intra-accumbal infusion of NNC711, but not of (S)-SNAP-5114, induced a dose-related increase in accumbal GABA efflux. These results provide in vivo evidence that GAT1, but not GAT3, plays an important role in regulation of accumbal extracellular GABA levels.

Free Research Field

口腔外科

Academic Significance and Societal Importance of the Research Achievements

麻薬性鎮痛薬が起こす多幸感や精神依存には，オピオイド受容体の選択的刺激を介した中脳辺縁系DA神経活動の亢進へ関与すると想定されている。このDA神経活動の促進は，GABA神経とDA神経との相互作用で起こることが考えられる。本研究は，中脳辺縁系DA神経が投射する側坐核のGABA神経活動の制御機構についてGABAを細胞内へ取り込むGATの役割の面から実験動物を用いて検討した。その結果，側坐核では細胞外へ放出されたGABAが，GAT3よりもGAT1を介して細胞内に取り込まれること示唆する結果がin vivoの条件下で得られたことが意義深い。