Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine

@article{Kelz1999ExpressionOT,
  title={Expression of the transcription factor $\Delta$FosB in the brain controls sensitivity to cocaine},
  author={Max B Kelz and Jingshan Chen and William A. Carlezon and Kim Whisler and Lauren Gilden and Alison M. Beckmann and Cathy Steffen and Ya-Jun Zhang and Louis A. Marotti and David W Self and Tatiana Tkatch and Gytis Baranauskas and Dalton James Surmeier and Rachael L. Neve and Ronald S. Duman and Marina R. Picciotto and Eric J. Nestler},
  journal={Nature},
  year={1999},
  volume={401},
  pages={272-276}
}
Acute exposure to cocaine transiently induces several Fos family transcription factors in the nucleus accumbens, a region of the brain that is important for addiction. In contrast, chronic exposure to cocaine does not induce these proteins, but instead causes the persistent expression of highly stable isoforms of ΔFosB. ΔFosB is also induced in the nucleus accumbens by repeated exposure to other drugs of abuse, including amphetamine, morphine, nicotine and phencyclidine. The sustained… 
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648 Citations
Highly Influential Citations
35
Background Citations
282
Methods Citations
40
Results Citations
18

648 Citations

Epigenetic Regulation of Hippocampal Fosb Expression Controls Behavioral Responses to Cocaine
TLDR
It is demonstrated that chronic cocaine engages locus-specific changes in the epigenetic profile of the FosB gene in the hippocampus, and that these alterations are required for cocaine-dependent gene expression and cocaine–environment associations.
Induction of nuclear factor‐κB in nucleus accumbens by chronic cocaine administration
TLDR
DNA microarray analysis is used to identify genes that are regulated in the nucleus accumbens upon ΔFosB expression in inducible bitransgenic mice and establish NF‐κB as a putative target for ΔFOSB and implicate NF‐kkB signaling pathways in the long‐term adaptations of nucleus Accumbens neurons to cocaine.
An essential role for ΔFosB in the nucleus accumbens in morphine action
TLDR
It is demonstrated that ΔFosB in the NAc, partly through the repression of dynorphin expression, mediates several major features of opiate addiction.
Distinct patterns of ΔFosB induction in brain by drugs of abuse
TLDR
It is shown that chronic, but not acute, administration of each of four drugs of abuse, cocaine, morphine, ethanol, and Δ9‐THC, robustly induces ΔFosB in nucleus accumbens, although different patterns in the core vs. shell subregions of this nucleus were apparent for the different drugs.
The dopamine D1 receptor is a critical mediator for cocaine‐induced gene expression
TLDR
It is found that there is a lack of induction of c‐Fos, FosB, Fra‐2 and JunB by acute cocaine exposure, and of ΔFosB by repeated cocaine administration in both the NAc and CPu of D1 receptor mutant mice compared with wild‐type control mice, suggesting that the D1 receptors is a critical mediator for cocaine‐induced expression of these genes.
Regulation of gene expression and cocaine reward by CREB and ΔFosB
TLDR
Using microarray analysis in the nucleus accumbens of inducible transgenic mice, it is found that CREB and a dominant-negative CREB have opposite effects on gene expression, as do prolonged expression of ΔFosB and the activator protein-1 (AP-1) antagonist ΔcJun.
Serum Response Factor and cAMP Response Element Binding Protein Are Both Required for Cocaine Induction of ΔFosB
TLDR
A necessary role for two transcription factors, cAMP response element binding protein (CREB) and serum response factor (SRF), in mediating ΔFosB induction within the mouse nucleus accumbens (NAc), a key brain reward region is demonstrated.
Effect of ΔFosB overexpression on opioid and cannabinoid receptor-mediated signaling in the nucleus accumbens
Upregulation of Npas4 protein expression by chronic administration of amphetamine in rat nucleus accumbens in vivo
Inducible, brain region-specific expression of a dominant negative mutant of c-Jun in transgenic mice decreases sensitivity to cocaine
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References

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