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Combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic-like effect synergistically

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Title: Combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic-like effect synergistically
Authors: An, Yan Browse this author
Inoue, Takeshi Browse this author →KAKEN DB
Kitaichi, Yuji Browse this author →KAKEN DB
Chen, Chong Browse this author
Nakagawa, Shin Browse this author →KAKEN DB
Wang, Ce Browse this author
Kusumi, Ichiro Browse this author →KAKEN DB
Keywords: Contextual fear conditioning
Lithium augmentation
Mirtazapine
Median raphe nucleus
Hippocampus
Amygdala
Issue Date: 15-Jul-2016
Publisher: Elsevier
Journal Title: European journal of pharmacology
Volume: 783
Start Page: 112
End Page: 116
Publisher DOI: 10.1016/j.ejphar.2016.05.004
PMID: 27154172
Abstract: Although preclinical and clinical studies have established the efficacy of lithium augmentation of antidepressant drugs, the mechanism of action of lithium augmentation is not fully understood. Our previous study reported that subchronic lithium treatment enhanced the anxiolytic-like effect of systemic mirtazapine. In the present study, we examined the effect of subchronic lithium in combination with acute local intracerebral injection of mirtazapine on fear-related behaviors in a contextual fear conditioning test in rats to clarify the target brain region of lithium augmentation of mirtazapine. After conditioning by footshock, diet (food pellets) containing Li2CO3 at a concentration of 0.2% was administered for 7 days. Ten min before testing and 7 days after conditioning, mirtazapine (3 μg/site) in a volume of 0.5 µl was acutely injected into the median raphe nucleus (MRN), hippocampus or amygdala. The combination of subchronic lithium and acute mirtazapine microinjection into the MRN but not the hippocampus or the amygdala reduced fear expression synergistically. These results suggest that intra-MRN mirtazapine treatment with subchronic lithium exerts the anxiolytic-like effect through the facilitation of the MRN-5HT pathway.
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/
https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/66615
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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