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Publication : Regulation of gene expression and cocaine reward by CREB and DeltaFosB.

First Author  McClung CA Year  2003
Journal  Nat Neurosci Volume  6
Issue  11 Pages  1208-15
PubMed ID  14566342 Mgi Jnum  J:92942
Mgi Id  MGI:3055239 Doi  10.1038/nn1143
Citation  McClung CA, et al. (2003) Regulation of gene expression and cocaine reward by CREB and DeltaFosB. Nat Neurosci 6(11):1208-15
abstractText  DeltaFosB (a truncated form of FosB) and CREB (cAMP response element binding protein) are transcription factors induced in the brain's reward pathways after chronic exposure to drugs of abuse. However, their mechanisms of action and the genes they regulate remain unclear. Using microarray analysis in the nucleus accumbens of inducible transgenic mice, we found that CREB and a dominant-negative CREB have opposite effects on gene expression, as do prolonged expression of DeltaFosB and the activator protein-1 (AP-1) antagonist DeltacJun. However, unlike CREB, short-term and prolonged DeltaFosB induction had opposing effects on gene expression. Gene expression induced by short-term DeltaFosB and by CREB was strikingly similar, and both reduced the rewarding effects of cocaine, whereas prolonged DeltaFosB expression increased drug reward. Gene expression after a short cocaine treatment was more dependent on CREB, whereas gene expression after a longer cocaine treatment became increasingly DeltaFosB dependent. These findings help define the molecular functions of CREB and DeltaFosB and identify clusters of genes that contribute to cocaine addiction.
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