D1 dopamine receptor activation of NFAT-mediated striatal gene expression
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...
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Published in | The European journal of neuroscience Vol. 27; no. 1; pp. 31 - 42 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Publishing Ltd
01.01.2008
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Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ArticleID:EJN5980 ark:/67375/WNG-FCQL9KXC-2 istex:DFA232D015AA24F294CA4891F77C1F70DE03369B Stem Cell Research Program, University of Wisconsin‐Madison, T680 Waisman Center, 1500 Highland Avenue, Madison, WI 53705‐2280, USA R.D.G. and J.P.W. contributed equally to this work. Present address Department of Molecular and Cellular Physiology, Stanford University, Beckman Center, B101, 279 Campus Drive, Stanford, CA 94305, USA ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0953-816X 1460-9568 |
DOI: | 10.1111/j.1460-9568.2007.05980.x |