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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-1-10
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pubmed:abstractText |
Exposure to drugs of abuse activates gene expression and protein synthesis that result in long-lasting adaptations in striatal signaling. Therefore, identification of the transcription factors that couple drug exposure to gene expression is of particular importance. Members of the nuclear factor of activated T-cells (NFATc) family of transcription factors have recently been implicated in shaping neuronal function throughout the rodent nervous system. Here we demonstrate that regulation of NFAT-mediated gene expression may also be a factor in drug-induced changes to striatal functioning. In cultured rat striatal neurons, stimulation of D1 dopamine receptors induces NFAT-dependent transcription through activation of L-type calcium channels. Additionally, the genes encoding inositol-1,4,5-trisphosphate receptor type 1 and glutamate receptor subunit 2 are regulated by striatal NFATc4 activity. Consistent with these in-vitro data, repeated exposure to cocaine triggers striatal NFATc4 nuclear translocation and the up-regulation of inositol-1,4,5-trisphosphate receptor type 1 and glutamate receptor subunit 2 gene expression in vivo, suggesting that cocaine-induced increases in gene expression may be partially mediated through activation of NFAT-dependent transcription. Collectively, these findings reveal a novel molecular pathway that may contribute to the enduring modifications in striatal functioning that occur following the administration of drugs of abuse.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Brain-Derived Neurotrophic Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Cocaine,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D1,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Amino-3-hydroxy-5-methyl-4-iso...,
http://linkedlifedata.com/resource/pubmed/chemical/enhanced green fluorescent protein,
http://linkedlifedata.com/resource/pubmed/chemical/glutamate receptor ionotropic...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1460-9568
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
31-42
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pubmed:meshHeading |
pubmed-meshheading:18184313-Animals,
pubmed-meshheading:18184313-Animals, Newborn,
pubmed-meshheading:18184313-Brain-Derived Neurotrophic Factor,
pubmed-meshheading:18184313-Cells, Cultured,
pubmed-meshheading:18184313-Chromatin Immunoprecipitation,
pubmed-meshheading:18184313-Cocaine,
pubmed-meshheading:18184313-Corpus Striatum,
pubmed-meshheading:18184313-Dopamine Uptake Inhibitors,
pubmed-meshheading:18184313-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:18184313-Excitatory Amino Acid Agonists,
pubmed-meshheading:18184313-Gene Expression,
pubmed-meshheading:18184313-Green Fluorescent Proteins,
pubmed-meshheading:18184313-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:18184313-Male,
pubmed-meshheading:18184313-Membrane Potentials,
pubmed-meshheading:18184313-Mice,
pubmed-meshheading:18184313-Mice, Inbred C57BL,
pubmed-meshheading:18184313-NFATC Transcription Factors,
pubmed-meshheading:18184313-Rats,
pubmed-meshheading:18184313-Receptors, AMPA,
pubmed-meshheading:18184313-Receptors, Dopamine D1,
pubmed-meshheading:18184313-Transfection,
pubmed-meshheading:18184313-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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pubmed:year |
2008
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pubmed:articleTitle |
D1 dopamine receptor activation of NFAT-mediated striatal gene expression.
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pubmed:affiliation |
Department of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street, S.E., Minneapolis, MN 55455, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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