Abstract
Drug addiction involves compulsive drug-seeking and drug-taking despite known adverse consequences. The enduring nature of drug addiction suggests that repeated exposure to abused drugs leads to stable alterations that likely involve changes in gene expression in the brain. The dopamine D1 receptor has been shown to mediate the long-term behavioral effects of cocaine. To examine how the persistent behavioral effects of cocaine correlate with underlying changes in gene expression, we have used D1 receptor mutant and wild-type mice to identify chronic cocaine-induced gene expression changes mediated via the D1 receptors. We focused on the caudoputamen and nucleus accumbens, two key brain regions that mediate the long-term effects of cocaine. Our analyses demonstrate that repeated cocaine administration induces changes in the expression of 109 genes, including those encoding the stromal cell-derived factor 1, insulin-like growth factor binding protein 6, sigma 1 receptor, regulators of G-protein signaling protein 4, Wnt1 responsive Cdc42 homolog, Ca2+/calmodulin- dependent protein kinase II α subunit, and cyclin D2, via the D1 receptors. Moreover, the seven genes contain AP-1 binding sites in their promoter regions. These results suggest that genes encoding certain extracellular factors, membrane receptors and modulators, and intracellular signaling molecules, among others, are regulated by cocaine via the D1 receptor, and these AP-1 transcription complex-regulated genes might contribute to persistent cocaine-induced behavioral changes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1443-1454 |
| Number of pages | 12 |
| Journal | Neuropsychopharmacology |
| Volume | 30 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2005 |
| Externally published | Yes |
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Keywords
- AP-1 transcription complex
- Chronic cocaine
- Dopamine D1 receptor
- Gene expression
ASJC Scopus subject areas
- Pharmacology
Cite this
Repeated cocaine administration induces gene expression changes through the dopamine D1 receptors. / Zhang, Dongsheng; Zhang, Lu; Tang, Yang; Zhang, Qi; Lou, Danwen; Sharp, Frank R; Zhang, Jianhua; Xu, Ming.
In: Neuropsychopharmacology, Vol. 30, No. 8, 08.2005, p. 1443-1454.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Repeated cocaine administration induces gene expression changes through the dopamine D1 receptors
AU - Zhang, Dongsheng
AU - Zhang, Lu
AU - Tang, Yang
AU - Zhang, Qi
AU - Lou, Danwen
AU - Sharp, Frank R
AU - Zhang, Jianhua
AU - Xu, Ming
PY - 2005/8
Y1 - 2005/8
N2 - Drug addiction involves compulsive drug-seeking and drug-taking despite known adverse consequences. The enduring nature of drug addiction suggests that repeated exposure to abused drugs leads to stable alterations that likely involve changes in gene expression in the brain. The dopamine D1 receptor has been shown to mediate the long-term behavioral effects of cocaine. To examine how the persistent behavioral effects of cocaine correlate with underlying changes in gene expression, we have used D1 receptor mutant and wild-type mice to identify chronic cocaine-induced gene expression changes mediated via the D1 receptors. We focused on the caudoputamen and nucleus accumbens, two key brain regions that mediate the long-term effects of cocaine. Our analyses demonstrate that repeated cocaine administration induces changes in the expression of 109 genes, including those encoding the stromal cell-derived factor 1, insulin-like growth factor binding protein 6, sigma 1 receptor, regulators of G-protein signaling protein 4, Wnt1 responsive Cdc42 homolog, Ca2+/calmodulin- dependent protein kinase II α subunit, and cyclin D2, via the D1 receptors. Moreover, the seven genes contain AP-1 binding sites in their promoter regions. These results suggest that genes encoding certain extracellular factors, membrane receptors and modulators, and intracellular signaling molecules, among others, are regulated by cocaine via the D1 receptor, and these AP-1 transcription complex-regulated genes might contribute to persistent cocaine-induced behavioral changes.
AB - Drug addiction involves compulsive drug-seeking and drug-taking despite known adverse consequences. The enduring nature of drug addiction suggests that repeated exposure to abused drugs leads to stable alterations that likely involve changes in gene expression in the brain. The dopamine D1 receptor has been shown to mediate the long-term behavioral effects of cocaine. To examine how the persistent behavioral effects of cocaine correlate with underlying changes in gene expression, we have used D1 receptor mutant and wild-type mice to identify chronic cocaine-induced gene expression changes mediated via the D1 receptors. We focused on the caudoputamen and nucleus accumbens, two key brain regions that mediate the long-term effects of cocaine. Our analyses demonstrate that repeated cocaine administration induces changes in the expression of 109 genes, including those encoding the stromal cell-derived factor 1, insulin-like growth factor binding protein 6, sigma 1 receptor, regulators of G-protein signaling protein 4, Wnt1 responsive Cdc42 homolog, Ca2+/calmodulin- dependent protein kinase II α subunit, and cyclin D2, via the D1 receptors. Moreover, the seven genes contain AP-1 binding sites in their promoter regions. These results suggest that genes encoding certain extracellular factors, membrane receptors and modulators, and intracellular signaling molecules, among others, are regulated by cocaine via the D1 receptor, and these AP-1 transcription complex-regulated genes might contribute to persistent cocaine-induced behavioral changes.
KW - AP-1 transcription complex
KW - Chronic cocaine
KW - Dopamine D1 receptor
KW - Gene expression
UR - http://www.scopus.com/inward/record.url?scp=23844481457&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23844481457&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1300680
DO - 10.1038/sj.npp.1300680
M3 - Article
C2 - 15770241
AN - SCOPUS:23844481457
VL - 30
SP - 1443
EP - 1454
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 8
ER -