title: Microinjection of sanguinarine into the ventrolateral orbital cortex inhibits Mkp-1 and exerts an antidepressant-like effect in rats.
abstract: 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 ERK (ratio of phosphor-ERK to ERK) were also examined by immunoblotting. A single bilateral intra-VLO infusion of SA (2.5, 5 or 10 μg/0.5 μl 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.
authors.affiliation: Department of Psychosomatics, Xi'jing Hospital, Fourth Military Medical University, 17 Chang'le West Road, Xi'an 710032, China.
authors.forename: Yunchun
authors.initials: Y
authors.lastname: Chen
authors.forename: Huaning
authors.initials: H
authors.lastname: Wang
authors.forename: Ruiguo
authors.initials: R
authors.lastname: Zhang
authors.forename: Huaihai
authors.initials: H
authors.lastname: Wang
authors.forename: Zhengwu
authors.initials: Z
authors.lastname: Peng
authors.forename: Runzhu
authors.initials: R
authors.lastname: Sun
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Tan
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D053119:Benzophenanthridines / Q000008:administration & dosage*; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D054638:Dual Specificity Phosphatase 1 / Q000096:biosynthesis*; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D008845:Microinjections; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000928:Antidepressive Agents; D053119:Benzophenanthridines; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; C005705:sanguinarine; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat