Activity-Related Transcription: Role in Addiction

This chapter explores activity-dependent transcriptional changes in neurons following exposure to psychostimulants or opioids. We begin with a discussion of how these drugs of abuse trigger immediate early gene (IEG) expression by detailing their pharmacological activities and the distribution of their receptors in brain regions associated with reward and memory. We then present evidence from numerous studies showing that changes in IEG expression indicate drug-responsive activity in specific neuronal populations involved in behavioral regulation. Following this, we describe the signaling cascades that are activated for the transcriptional regulation of IEGs. Additionally, we explain how these IEGs often encode transcription factors that orchestrate a subsequent wave of transcriptional plasticity. This second wave involves delayed secondary response genes (DSRGs) that mediate changes in synaptic structure and function. Lastly, we discuss technical advancements in transcriptomic analysis, including RNA-sequencing technologies, single-cell and single-nucleus RNA sequencing, and spatial transcriptomics, highlighting how these innovations have enhanced our understanding of drug-induced transcriptional changes in neurons.