Alternative splicing is a co-transcriptional process that significantly contributes to the molecular landscape of the cell. It plays a multifaceted role in shaping gene transcription, protein diversity, and functional adaptability in response to environmental cues. Recent studies demonstrate that drugs of abuse have a profound impact on alternative splicing patterns within different brain regions. Drugs like alcohol and cocaine modify the expression of genes responsible for encoding splicing factors, thereby influencing alternative splicing of crucial genes involved in neurotransmission, neurogenesis, and neuroinflammation. Notable examples of these alterations include alcohol-induced changes in splicing factors such as HSPA6 and PCBP1, as well as cocaine's impact on PTBP1 and SRSF11. Beyond the immediate effects of drug exposure, recent research has shed light on the role of alternative splicing in contributing to the risk of substance use disorders (SUDs). This is exemplified by exon skipping events in key genes like ELOVL7, which can elevate the risk of alcohol use disorder. Lastly, drugs of abuse can induce splicing alterations through epigenetic modifications. For example, cocaine exposure leads to alterations in levels of trimethylated lysine 36 of histone H3, which exhibits a robust association with alternative splicing and serves as a reliable predictor for exon exclusion. In summary, alternative splicing has emerged as a critical player in the complex interplay between drugs of abuse and the brain, offering insights into the molecular underpinnings of SUDs.

选择性剪接是一种共转录过程，对细胞的分子景观有显着贡献。它在塑造基因转录、蛋白质多样性和响应环境线索的功能适应性方面发挥着多方面的作用。最近的研究表明，滥用药物对不同大脑区域内的选择性剪接模式具有深远的影响。酒精和可卡因等药物会改变负责编码剪接因子的基因的表达，从而影响涉及神经传递、神经发生和神经炎症的关键基因的选择性剪接。这些改变的显着例子包括酒精引起的剪接因子（例如 HSPA6 和 PCBP1）的变化，以及可卡因对 PTBP1 和 SRSF11 的影响。除了药物暴露的直接影响之外，最近的研究还揭示了选择性剪接在增加物质使用障碍 (SUD) 风险中的作用。ELOVL7等关键基因中的外显子跳跃事件就证明了这一点，这可能会增加酒精使用障碍的风险。最后，滥用药物可以通过表观遗传修饰诱导剪接改变。例如，接触可卡因会导致组蛋白 H3 的三甲基化赖氨酸 36 水平发生变化，这与选择性剪接表现出强烈的相关性，并可作为外显子排除的可靠预测因子。总之，选择性剪接已成为滥用药物与大脑之间复杂相互作用的关键参与者，为了解 SUD 的分子基础提供了见解。