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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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Title: Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats
Authors: An, Yan Browse this author
Chen, Chong Browse this author
Inoue, Takeshi Browse this author →KAKEN DB
Nakagawa, Shin Browse this author →KAKEN DB
Kitaichi, Yuji Browse this author →KAKEN DB
Wang, Ce Browse this author
Izumi, Takeshi Browse this author →KAKEN DB
Kusumi, Ichiro Browse this author →KAKEN DB
Keywords: Contextual fear conditioning
Hippocampus
Median raphe nucleus
Serotonin
5-HT1A receptor
Issue Date: 3-Oct-2016
Publisher: Elsevier
Journal Title: Progress in neuro-psychopharmacology & biological psychiatry
Volume: 70
Start Page: 17
End Page: 23
Publisher DOI: 10.1016/j.pnpbp.2016.04.014
PMID: 27137833
Abstract: 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/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/67247
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 久住 一郎

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