Serum Response Factor and cAMP Response Element Binding Protein Are Both Required for Cocaine Induction of ΔFosB

• DOI: 10.1523/jneurosci.1381-12.2012
• Publication Date: 2012-05-30T18:59:42Z
• Authors: Vincent Vialou; Jian Feng; Alfred J. Robison; Stacy M. Ku; Deveroux Ferguson; Kimberly N. Scobie; Michelle S. Mazei...; Ezekiell Mouzon; Eric J. Nestler
• Keywords: FOSB; Conditioned place preference; Response element

The molecular mechanism underlying induction by cocaine of ΔFosB, a transcription factor important for addiction, remains unknown. Here, we demonstrate necessary role two factors, cAMP response element binding protein (CREB) and serum (SRF), in mediating this within the mouse nucleus accumbens (NAc), key brain reward region. CREB SRF are both activated NAc bind to fosB gene promoter. Using viral-mediated Cre recombinase expression single- or double-floxed mice, show that deletion factors from region completely blocks ΔFosB NAc, whereas either alone has no effect. Furthermore, renders animals less sensitive rewarding effects moderate doses when tested conditioned place preference (CPP) procedure also locomotor sensitization higher cocaine. Deletion opposite effect enhances CPP sensitization. In contrast cocaine, chronic social stress, which have shown previously requires activation SRF, is unaffected alone. These surprising findings involvement distinct transcriptional mechanisms same versus stress. Our results establish complex mode regulation concerted activities CREB.