Transcriptomics and Cocaine Addiction

Repeated cocaine use represents a severe environmental insult to the brain, one which induces compensatory responses, much of which happen at the level of gene transcription. In most people, this response is adaptive, but in a minority of people – those susceptible to substance use disorders – this plasticity turns maladaptive. The goal of transcriptomics relating to cocaine use is to employ a relatively unbiased discovery-based approach to identify novel proximal mechanisms for the maladaptive plasticity. Not surprisingly, the search is complicated by the fact that adaptive neuroplasticity is a large and dynamic set of responses, and it is almost certain that there are multiple subtypes of cocaine use disorders driven by different mechanisms in different brain regions. When surveying the transcriptomics of cocaine, the most notable, rapid, and robust transcriptional regulation happens in transcripts regulating transcription. These include transcripts for transcription factors and epigenetic histone-related enzymes, both classes representing distal (i.e., upstream) mechanisms. As proximal mechanisms come to light, it has become evident that cocaine-induced transcriptional changes are widespread and affect many systems. The use of transcriptomic techniques and bioinformatics tools holds great promise in advancing our knowledge of cocaine-induced transcriptomic changes and identifying targets viable for pharmaceutical treatment.