Insight into Cocaine-Induced Neural and Behavioral Adaptations Using Genome-Wide Expression Profiling and Epigenomic Analysis

Sumana      Chakravarty; Arvind      Kumar

Abstract

Cocaine, like most other drugs of abuse, exerts long lasting changes in gene expression in the reward circuitry of the brain. This resultant remodelled reward circuitry is considered to underlie drug addiction and relapse. In recent years, genome-wide expression studies and epigenomic analysis of the affected regions in the reward circuitry have identified molecular changes associated with the structural remodeling of the circuitry. In particular, application of gene expression microarray and chromatin immunoprecipitation (ChIP) coupled to microarray (ChIP-chip) or sequencing (ChIP-seq) has provided unprecedented insights into the neural and behavioral adaptations in nucleus accumbens (NAc), the critical substrate of the reward circuitry, in cocaine addiction. Genome level expression profiling and epigenomic analysis leading to the recent advances in our understanding of cocaine-induced neural and behavioral adaptations are reviewed here. We examine the convergence of transcriptomic and epigenomic evidence, and discuss about emerging drug target candidates in cocaine-addiction.

Keywords: Addiction, nucleus accumbens, reward circuitry, gene regulatory networks, microarray, ChIP-chip, ChIP-Seq, RNA-Seq, mesolimbic dopamine, cocaine addiction, transcription, oligonucleotide microarrays, post-translational modifications, epigenetic regulatory mechanisms, accumbens genome