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Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats

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タイトル: Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats
著者: An, Yan 著作を一覧する
Chen, Chong 著作を一覧する
Inoue, Takeshi 著作を一覧する
Nakagawa, Shin 著作を一覧する
Kitaichi, Yuji 著作を一覧する
Wang, Ce 著作を一覧する
Izumi, Takeshi 著作を一覧する
Kusumi, Ichiro 著作を一覧する
キーワード: Contextual fear conditioning
Hippocampus
Median raphe nucleus
Serotonin
5-HT1A receptor
発行日: 2016年10月 3日
出版者: Elsevier
誌名: Progress in neuro-psychopharmacology & biological psychiatry
巻: 70
開始ページ: 17
終了ページ: 23
出版社 DOI: 10.1016/j.pnpbp.2016.04.014
抄録: The functional role of serotonergic projections from the median raphe nucleus (MRN) to the dorsal hippocampus (DH) in anxiety remains understood poorly. The purpose of the present research was to examine the functional role of this pathway, using the contextual fear conditioning (CFC) model of anxiety. We show that intra-MRN microinjection of mirtazapine, a noradrenergic and specific serotonergic antidepressant, reduced freezing in CFC without affecting general motor activity dose-dependently, suggesting an anxiolytic-like effect. In addition, intra-MRN microinjection of mirtazapine dose-dependently increased extracellular concentrations of serotonin (5-HT) but not dopamine in the DH. Importantly, intra-DH pre-microinjection of WAY-100635, a 5-HT1A antagonist, significantly attenuated the effect of mirtazapine on freezing. These results, for the first time, suggest that activation of the MRN-DH 5-HT1A pathway exerts an anxiolytic-like effect in CFC. This is consistent with the literature that the hippocampus is essential for retrieval of contextual memory and that 5-HT1A receptor activation in the hippocampus primarily exerts an inhibitory effect on the neuronal activity.
Rights: © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
資料タイプ: article (author version)
URI: http://hdl.handle.net/2115/67247
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 久住 一郎

 

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