Browse

Dose-dependent effect of intracerebroventricular injection of ouabain on the phosphorylation of the MEK1/2-ERK1/2-p90RSK pathway in the rat brain related to locomotor activity

Cited 38 time in Web of Science Cited 39 time in Scopus
Issue Date
2008-07-02
Publisher
Elsevier
Citation
Prog Neuropsychopharmacol Biol Psychiatry. 2008 ;32(7):1637-42.
Keywords
AnimalsBehavior, Animal/drug effectsBrain/drug effects/*enzymologyDose-Response Relationship, DrugEnzyme Inhibitors/*pharmacologyExtracellular Signal-Regulated MAP Kinases/*metabolismGene Expression Regulation, Enzymologic/drug effectsInjections, Intraventricular/methodsMaleMotor Activity/*drug effectsOuabain/*pharmacologyPhosphorylation/drug effectsRatsRats, Sprague-DawleySignal Transduction/*drug effects
Abstract
Intracerebroventricular (ICV) injection of ouabain, a specific Na-K ATPase inhibitor, induced behavioral changes in rats, a putative animal model for bipolar disorder. The binding of ouabain to Na-K ATPase is known to affect signaling molecules in vitro such as extracellular signal-regulated kinase1/2 (ERK1/2). Although ERK has been suggested to be related to the behavioral alterations induced by various psychotomimetics, the effect of ouabain on ERK in the brain related to behavioral changes has not been examined. After ICV injection of ouabain in rats, we investigated changes in the phosphorylation of mitogen-activated protein kinase kinase1/2 (MEK1/2), ERK1/2, and p90 ribosomal s6 kinase (p90RSK) in rat striatum, frontal cortex, and hippocampus along with changes in locomotor activity. Ouabain induced the following biphasic dose-dependent changes in locomotor activity: no change with 10(-6) M, a statistically significant decrease with 10(-5) M, no change with 10(-4) M, and a statistically significant increase with 0.5x10(-3) and 10(-3) M. The phosphorylation level of MEK1/2, ERK1/2, and p90RSK in rat striatum showed dose-dependent changes similar to those observed in locomotor activity with relatively high correlation. The phosphorylation of these molecules in rat frontal cortex and hippocampus also changed in a similar dose-dependent pattern. Taken together, ouabain induced biphasic dose-dependent changes in locomotor activity and the phosphorylation of the ERK1/2 pathway. These findings suggest a possible relationship between ouabain-induced behavioral changes and ERK activity in the brain and suggest an important role of ERK in regulating locomotor activity and mood state.
ISSN
0278-5846 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18590792

https://hdl.handle.net/10371/63321
DOI
https://doi.org/10.1016/j.pnpbp.2008.05.027
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Psychiatry (정신과학전공)Journal Papers (저널논문_정신과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse