D1 dopamine receptor activation of NFAT-mediated striatal gene expression

Rachel D. Groth, Jason P. Weick, Katherine C. Bradley, Jessie I. Luoma, Bharathi Aravamudan, Jason R. Klug, Mark J. Thomas, Paul G. Mermelstein

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31-42
Number of pages12
JournalEuropean Journal of Neuroscience
Volume27
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Glutamate receptor subunit 2
  • Inositol-1, 4, 5-trisphosphate receptor type 1
  • Mouse
  • Nuclear factor of activated T-cells 4
  • Rat
  • Striatum

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