Opioid-induced structural and functional plasticity of medium-spiny neurons in the nucleus accumbens

Opioid Use Disorder (OUD) is a chronic relapsing clinical condition with tremendous morbidity and mortality that frequently persists, despite treatment, due to an individual's underlying psychological, neurobiological, and genetic vulnerabilities. Evidence suggests that these vulnerabilities may have neurochemical, cellular, and molecular bases. Key neuroplastic events within the mesocorticolimbic system that emerge through chronic expo sure to opioids may have a determinative influence on behavioral symptoms associated with OUD. In particular, structural and functional alterations in the dendritic spines of medium spiny neurons (MSNs) within the nucleus accumbens (NAc) and its dopaminergic projections from the ventral tegmental area (VTA) are believed to facilitate these behavioral sequelae. Additionally, glutamatergic neurons from the prefrontal cortex, the basolateral amygdala, the hippocampus, and the thalamus project to these same MSNs, providing an enriched target for synaptic plasticity. Here, we review literature related to neuroadaptations in NAc MSNs from dopaminergic and glutamatergic pathways in OUD. We also describe new findings related to transcriptional, epigenetic, and molecular mechanisms in MSN plasticity in the different stages of OUD.