Epigenetic Priming of Activity-Dependent Transcription in Drug Addiction

Chronic exposure to drugs of abuse can cause profound and persistent alterations in the brain, particularly in the nucleus accumbens, which is a key brain reward region. These changes include variations in gene expression, neuronal morphology, and synaptic function that play critical roles in the development and maintenance of addiction. This chapter delves into the emerging field of epigenetic priming in drug addiction, focusing on chromatin-based mechanisms—so-called “chromatin scars”—that underlie the transition from recreational drug use to compulsive drug-seeking behavior, and how activity-dependent transcription contributes to the development of substance use disorders (SUDs). We then review the role of epigenetic regulation, such as DNA methylation and histone modifications, in mediating transcriptional changes and the consequent neural plasticity associated with addiction. Furthermore, we discuss the implications of these insights for understanding addiction as a complex and multifaceted disorder, and the potential of targeted epigenetic therapies for SUDs.