Linked Life Data

12486182

Source:http://linkedlifedata.com/resource/pubmed/id/12486182

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2002-12-17
pubmed:abstractText
The cAMP response element-binding protein (CREB) is a critical integrator of neural plasticity that is responsive in a brain region-specific manner to a variety of environmental and pharmacological stimuli, including widely prescribed antidepressant medications. We developed inducible transgenic lines of mice that express either CREB or a dominant-negative mutant of CREB (mCREB) in forebrain regions and used these mice to determine the functional significance of this transcription factor in the learned helplessness paradigm, a behavioral model of depression. We also use a complementary viral-mediated gene transfer approach to directly test the effect of mCREB in the nucleus accumbens, a brain region important for motivation and reward. The results demonstrate that blockade of CREB by overexpression of mCREB in transgenic mice or by viral expression of mCREB in the nucleus accumbens produces an antidepressant-like effect, whereas overexpression of CREB in transgenic mice results in the opposite phenotype. In addition, mCREB expression was colocalized with and decreased the expression of prodynorphin in nucleus accumbens medium spiny neurons, and antagonism of dynorphin in the nucleus accumbens was sufficient to produce an antidepressant-like effect similar to that observed after blockade of CREB. Together, the results demonstrate that nucleus accumbens CREB-dynorphin influence behavior in the learned helplessness model and suggest that this signaling cascade may contribute to symptoms of depression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10883-90
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12486182-Animals, pubmed-meshheading:12486182-Antidepressive Agents, pubmed-meshheading:12486182-Behavior, Animal, pubmed-meshheading:12486182-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:12486182-Depression, pubmed-meshheading:12486182-Dynorphins, pubmed-meshheading:12486182-Enkephalins, pubmed-meshheading:12486182-Helplessness, Learned, pubmed-meshheading:12486182-Immunohistochemistry, pubmed-meshheading:12486182-Male, pubmed-meshheading:12486182-Mice, pubmed-meshheading:12486182-Mice, Transgenic, pubmed-meshheading:12486182-Mutation, pubmed-meshheading:12486182-Naltrexone, pubmed-meshheading:12486182-Nucleus Accumbens, pubmed-meshheading:12486182-Prosencephalon, pubmed-meshheading:12486182-Protein Precursors, pubmed-meshheading:12486182-Rats, pubmed-meshheading:12486182-Rats, Sprague-Dawley, pubmed-meshheading:12486182-Receptors, Opioid, kappa
pubmed:year
2002
pubmed:articleTitle
Inhibition of cAMP response element-binding protein or dynorphin in the nucleus accumbens produces an antidepressant-like effect.
pubmed:affiliation
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't