依存性薬物による脳幹コリン作動性ニューロンでの新規シナプス可塑性とその意義の解明

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Author: 金田, 勝幸ほか

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Publication date: 2015-06-10

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Note (General)：: 金沢大学医薬保健研究域薬学系コカインを含む薬物による依存形成に腹側被蓋野（VTA）から側坐核および内側前頭前野に至る中脳辺縁皮質ドパミン神経系の活動と可塑的変化が重要な役割を果たすことが知られている。しかし，報酬系に投射し，その活動制御に関わるとされる報酬系外の神経核の関与やそこでのコカインによる可...

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Material Type: 文書・図像類
Title: 依存性薬物による脳幹コリン作動性ニューロンでの新規シナプス可塑性とその意義の解明
Author/Editor: 金田, 勝幸
Kaneda, Katsuyuki
Author Heading: 金田, 勝幸
Kaneda, Katsuyuki
Publication Date: 2015-06-10
Publication Date (W3CDTF): 2015-06-10
Alternative Title: Mechanisms and functional roles of drug-induced neuroplasticity in the brainstem cholinergic neurons
Periodical title: 平成26(2014)年度科学研究費補助金基盤研究(C) 研究成果報告書 = 2014 Fiscal Year Final Research Report
No. or year of volume/issue: 2012-04-01 - 2015-03-31
Volume: 2012-04-01 - 2015-03-31
Pages: 6p.-
Text Language Code: jpn
Subject Heading: 薬物依存
神経可塑性
背外側被蓋核
腹側被蓋野
報酬系
Target Audience: 一般
Note (General): 金沢大学医薬保健研究域薬学系
コカインを含む薬物による依存形成に腹側被蓋野（VTA）から側坐核および内側前頭前野に至る中脳辺縁皮質ドパミン神経系の活動と可塑的変化が重要な役割を果たすことが知られている。しかし，報酬系に投射し，その活動制御に関わるとされる報酬系外の神経核の関与やそこでのコカインによる可塑的変化の誘導については不明であった。そこで我々は背外側被蓋核（LDT）に着目し、コカインによる依存形成における役割を解析したところ、LDTの神経活動およびLDTからVTAへのコリン作動性神経伝達がコカイン依存形成に関与すること、また、この過程にLDTコリン作動性ニューロンでのシナプス可塑性が関与する可能性を見出した。
The involvement and plasticity of the mesocorticolimbic dopamine (DA) system in cocaine-induced addiction have been studied extensively. However, it remains largely unexplored that the role of the brainstem cholinergic system in cocaine addiction. The laterodorsal tegmental nucleus (LDT) contains cholinergic neurons that innervate the ventral tegmental area (VTA) and is crucial for regulating the activity of VTA DA neurons, implying that LDT may also be associated with cocaine addiction. In this study, we found that cholinergic transmission from the LDT to the VTA is involved in acquisition and expression of cocaine-induced conditioned place preference and that, after repeated cocaine exposures, these neurons exhibit synaptic plasticity, which is dependent on NMDA receptor activation, nitric oxide production, and the activity of medial prefrontal cortex. The findings strongly suggest that LDT cholinergic neurons may be critically involved in developing cocaine-induced addiction.
研究課題/領域番号:24500432, 研究期間(年度):2012-04-01 - 2015-03-31
DOI: 10.24517/00050928
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=30421366
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24500432/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-24500432/24500432seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA