Linked Life Data

15935071

Source:http://linkedlifedata.com/resource/pubmed/id/15935071

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-6-6
pubmed:abstractText
Accumulating evidence indicates that antidepressants alter intracellular signalling mechanisms resulting in long-term synaptic alterations which probably account for the delay in clinical action of these drugs. Therefore, we investigated the effects of chronic fluoxetine administration on extracellular signal-regulated kinase (ERK) 1 and 2, a group of MAPKs that mediate signal transduction from the cell surface downstream to the nucleus. Our data demonstrate that 3-week fluoxetine treatment resulted in long-lasting reduction of phospho-ERK 1 and 2. Such an effect depends on the length of the treatment given that no changes were observed after a single drug injection or after 2 weeks of treatment and it is region specific, being observed in hippocampus and frontal cortex but not in striatum. Finally, phospho-ERK 1 and 2 were differently modulated within nucleus and cytosol in hippocampus but similarly reduced in the same compartments of the frontal cortex, highlighting the specific subcellular compartmentalization of fluoxetine. Conversely, imipramine did not reduce the hippocampal phosphorylation of both ERK subtypes whereas it selectively increased ERK 1 phosphorylation in the cytosolic compartment of frontal cortex suggesting a drug-specific effect on this intracellular target. These results point to modulation of phosphorylation, rather than altered expression, as the main target in the action of fluoxetine on this pathway. The reduction of ERK 1/2 function herein reported may be associated with the therapeutic effects of fluoxetine in the treatment of depression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1551-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Chronic fluoxetine administration inhibits extracellular signal-regulated kinase 1/2 phosphorylation in rat brain.
pubmed:affiliation
Center of Neuropharmacology, Department of Pharmacological Sciences, University of Milan, Milan, Italy.
pubmed:publicationType
Journal Article