期刊
NEUROSCIENCE LETTERS
卷 506, 期 2, 页码 327-331出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.11.038
关键词
Mkp-1; Sanguinarine; Ventrolateral orbital cortex; Antidepression; Microinjection
资金
- National Natural Science Foundation of China [30700259, 30870886]
- National Science and Technology Program of China [2009BAI77B06]
We investigated the antidepressant effects of bilateral intra-the ventrolateral orbital cortex (VLO) administration of sanguinarine (SA), a selective mitogen-activated protein kinase phosphatase-1 (Mkp-1) inhibitor, in rats that had been subjected to a forced swimming test (FST) which is a classic animal model of depression. The expression of Mkp-1 and activation of ERR (ratio of phosphor-ERK to ERK) were also examined by immunoblotting. A single bilateral intra-VLO infusion of SA (2.5, 5 or 10 mu g/0.5 mu l per side) significantly reduced immobility time in the FST in dose-dependent fashion, as compared to vehicle-treated controls. A similar antidepressant effect was also observed in rats systemically administered fluoxetine, a classic antidepressant. The effects observed in the FST could not be attributed to non-specific increases in activity as neither microinjection of SA into the VLO nor fluoxetine treatment altered the behavior of the rats during the locomotion test. In addition, a decrease in the expression of Mkp-1 and a correlative increase in ERK activation were involved in the antidepressant effects of the bilateral SA administration into the VLO. The results indicated that Mkp-1 within the VLO is involved in the process of depression and may be a potential target for therapeutic action of antidepressant treatment. Crown Copyright (C) 2011 Published by Elsevier Ireland Ltd. All rights reserved.
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