Nuclear Factor κB Signaling Regulates Neuronal Morphology and Cocaine Reward

• DOI: 10.1523/jneurosci.6173-08.2009
• Publication Date: 2009-03-18T18:50:31Z
• Authors: Scott J. Russo; Matthew B. Wilkinson; Michelle S. Mazei...; David M. Dietz; Ian Maze; Vaishnav Krishnan; William Renthal; Ami Graham; Shari G. Birnbaum; Thomas A. Green; Bruce Robison; Alan Lesselyong; Linda I. Perrotti; Carlos A. Bolaños; Arvind Kumar; Michael S. Clark; John F. Neumaier; Rachael L. Neve; Asha L. Bhakar; Philip A. Barker; Eric J. Nestler
• Keywords: Medium spiny neuron

Although chronic cocaine-induced changes in dendritic spines on nucleus accumbens (NAc) neurons have been correlated with behavioral sensitization, the molecular pathways governing these structural changes, and their resulting effects, are poorly understood. The transcription factor, nuclear factor kappa B (NFkappaB), is rapidly activated by diverse stimuli regulates expression of many genes known to maintain cell structure. Therefore, we evaluated role NFkappaB regulating spine medium spiny NAc rewarding effects cocaine. We show that cocaine induces NFkappaB-dependent NFkappaB-Lac transgenic mice. This induction activity accompanied increased several genes, promoters which chromatin modifications after exposure consistent transcriptional activation. To study functional significance this induction, used viral-mediated gene transfer express either a constitutively active or dominant-negative mutant Inhibitor kinase (IKKca IKKdn), normally activates signaling, NAc. found activation IKKca increases number neurons, whereas inhibition IKKdn decreases basal blocks increase Moreover, ability previous an animal's preference for Together, studies establish direct regulate plasticity