rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
2008-7-10
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pubmed:abstractText |
Dopamine receptor signaling exhibits prominent plasticity that is important for the pathogenesis of both addictive and movement disorders. Psychoactive stimulants that activate the dopamine D(1) receptor (Drd1a) induce the rapid phosphorylation and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in neurons of the nucleus accumbens and ventral striatum. This response is known to be dependent on the phosphatase inhibitor dopamine- and cAMP-regulated phosphoprotein-32 (DARPP-32) and appears critical for the sensitization of Drd1a responses that contributes to addiction. Loss of dopamine input to the striatum, as in models of Parkinson's disease (PD), also results in a sensitization of responses to dopamine agonists that is manifest by increased activation of ERK1/2 in the dorsal striatum. Here, we test whether DARPP-32 is required for sensitization of Drd1a responses in a PD model. In the normal dorsal striatum, there is minimal Drd1a-mediated activation of ERK1/2; however, in the PD model there is robust Drd1a-mediated activation of ERK1/2. In both wild-type and DARPP-32 knock-out mice, Drd1a robustly induces pERK1/2 throughout the dopamine-depleted striatum. These findings indicate that Drd1a sensitization relevant for PD occurs by a novel mechanism that does not require DARPP-32.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-10433257,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-11102476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-11691979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-12015240,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-12383780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-14586460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-14976517,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-15608059,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-16373455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-16776597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-16793877,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-16871540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-17596448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-7809078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-9311927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-9694658,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18614680-9786988
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amphetamine,
http://linkedlifedata.com/resource/pubmed/chemical/Cocaine,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine and cAMP-Regulated...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Levodopa,
http://linkedlifedata.com/resource/pubmed/chemical/Ppp1r1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D1,
http://linkedlifedata.com/resource/pubmed/chemical/dopamine D1A receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1529-2401
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7113-20
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:18614680-Amphetamine,
pubmed-meshheading:18614680-Animals,
pubmed-meshheading:18614680-Basal Ganglia,
pubmed-meshheading:18614680-Cocaine,
pubmed-meshheading:18614680-Corpus Striatum,
pubmed-meshheading:18614680-Dopamine Agonists,
pubmed-meshheading:18614680-Dopamine Uptake Inhibitors,
pubmed-meshheading:18614680-Dopamine and cAMP-Regulated Phosphoprotein 32,
pubmed-meshheading:18614680-Enzyme Activation,
pubmed-meshheading:18614680-Enzyme Inhibitors,
pubmed-meshheading:18614680-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:18614680-Gene Expression Regulation,
pubmed-meshheading:18614680-Green Fluorescent Proteins,
pubmed-meshheading:18614680-Levodopa,
pubmed-meshheading:18614680-Mice,
pubmed-meshheading:18614680-Mice, Inbred C57BL,
pubmed-meshheading:18614680-Mice, Knockout,
pubmed-meshheading:18614680-Neurons,
pubmed-meshheading:18614680-Receptors, Dopamine D1
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pubmed:year |
2008
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pubmed:articleTitle |
Differences between dorsal and ventral striatum in Drd1a dopamine receptor coupling of dopamine- and cAMP-regulated phosphoprotein-32 to activation of extracellular signal-regulated kinase.
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pubmed:affiliation |
Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, Maryland 20892, USA. gerfenc@mail.nih.gov
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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