Transcriptional mechanisms: underlying addiction-related structural plasticity

Drug addiction is marked by long-lasting changes in behavior that result, in part, from altered patterns of gene expression within limbic forebrain regions, such as the nucleus accumbens (NAc). These changes in gene transcription are coordinated by a complex series of histone modifications surrounding DNA that result in either repression or activation of gene expression. Recent evidence has identified a network of gene expression changes, regulated by the transcription factor DeltaFosB, which alter the structure and function of NAc medium spiny neurons to control addictive-like behavior. In this review, we will discuss recent advances in our understanding of chromatin regulation by cocaine, as well as the consequences of such regulation on structural plasticity and its functional relevance to drug addiction.