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- Title
D1 dopamine receptor activation of NFAT-mediated striatal gene expression.
- Authors
Groth, Rachel D.; Weick, Jason P.; Bradley, Katherine C.; Luoma, Jessie I.; Aravamudan, Bharathi; Klug, Jason R.; Thomas, Mark J.; Mermelstein, Paul G.
- 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.
- Subjects
GENE expression; GENETIC regulation; DRUG abuse; BIOGENIC amines; PSYCHIATRIC drugs; NERVOUS system
- Publication
European Journal of Neuroscience, 2008, Vol 27, Issue 1, p31
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2007.05980.x