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 exposure 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.

阿片类药物使用障碍 (OUD) 是一种慢性复发性临床病症，具有极高的发病率和死亡率，尽管经过治疗，但由于个人潜在的心理、神经生物学和遗传脆弱性，这种病症经常持续存在。有证据表明，这些脆弱性可能具有神经化学、细胞和分子基础。通过长期接触阿片类药物而出现的中皮质边缘系统内的关键神经塑性事件可能对与 OUD 相关的行为症状产生决定性影响。特别是，伏隔核（NAc）内中型多棘神经元（MSN）树突棘的结构和功能改变及其腹侧被盖区（VTA）的多巴胺能投射被认为促进了这些行为后遗症。此外，来自前额皮质、基底外侧杏仁核、海马和丘脑的谷氨酸能神经元投射到这些相同的 MSN，为突触可塑性提供了丰富的目标。在这里，我们回顾了 OUD 中多巴胺能和谷氨酸能通路中 NAc MSN 神经适应的相关文献。我们还描述了 OUD 不同阶段 MSN 可塑性的转录、表观遗传和分子机制相关的新发现。