Induction of nuclear factor-kappa B 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 r elated striatal regions, brain regions that are important for the behaviora l effects of these drugs. To better understand the mechanisms by which Delt a FosB contributes to the effects of chronic drug treatment, we used DNA mi croarray analysis to identify genes that are regulated in the nucleus accum bens upon Delta FosB expression in inducible bitransgenic mice. One of the most highly regulated genes was that encoding a subunit of another transcri ption factor, nuclear factor-kappaB (NF-kappaB). Subsequent experiments con firmed the induction of NF-kappaB in the nucleus accumbens of mice overexpr essing Delta FosB as well as in wild-type mice treated chronically, but not acutely, with cocaine. These results establish NF-kappaB as a putative tar get for Delta FosB and implicate NF-kappaB signaling pathways in the long-t erm adaptations of nucleus accumbens neurons to cocaine.