Induction of nuclear factor-κB in nucleus accumbens by chronic cocaine administration

Delta FosB is a Fos family transcription factor that is induced by chronic exposure to cocaine and other drugs of abuse in the nucleus accumbens and related striatal regions, brain regions that are important for the behavioral effects of these drugs. To better understand the mechanisms by which Delta FosB contributes to the effects of chronic drug treatment, we used DNA microarray analysis to identify genes that are regulated in the nucleus accumbens upon Delta FosB expression in inducible bitransgenic mice. One of the most highly regulated genes was that encoding a subunit of another transcription factor, nuclear factor-kappaB (NF-kappaB). Subsequent experiments confirmed the induction of NF-kappaB in the nucleus accumbens of mice overexpressing Delta FosB as well as in wild-type mice treated chronically, but not acutely, with cocaine. These results establish NF-kappaB as a putative target for Delta FosB and implicate NF-kappaB signaling pathways in the long-term adaptations of nucleus accumbens neurons to cocaine.