Microinjection of sanguinarine into the ventrolateral orbital cortex inhibits Mkp-1 and exerts an antidepressant-like effect in rats

Neurosci Lett. 2012 Jan 11;506(2):327-31. doi: 10.1016/j.neulet.2011.11.038. Epub 2011 Dec 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage*
  • Benzophenanthridines / administration & dosage*
  • Blotting, Western
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism*
  • Depression / metabolism*
  • Disease Models, Animal
  • Dual Specificity Phosphatase 1 / biosynthesis*
  • Injections, Intraventricular
  • Isoquinolines / administration & dosage*
  • Male
  • Microinjections
  • Protein Kinase Inhibitors / administration & dosage
  • Rats
  • Rats, Sprague-Dawley


  • Antidepressive Agents
  • Benzophenanthridines
  • Isoquinolines
  • Protein Kinase Inhibitors
  • sanguinarine
  • Dual Specificity Phosphatase 1
  • Dusp1 protein, rat