Relapse to addictive drug use remains a major medical problem worldwide. In rodents, glutamate release in the nucleus accumbens core triggers reinstated drug seeking in response to stress, and drug-associated cues and contexts. Glutamatergic dysregulation in addiction results in part from long-lasting adaptations in accumbens astroglia, including downregulation of the glutamate transporter GLT-1 and retraction from synapses after withdrawal from psychostimulants and opioids. While their capacity to clear glutamate is disrupted by drug use and withdrawal, accumbens astrocytes undergo rapid, transient plasticity in response to drug-associated cues that reinstate seeking. Cued reinstatement of heroin seeking, for example, restores synaptic proximity of astrocyte processes through ezrin phosphorylation, and enhances GLT-1 surface expression. These adaptations limit drug seeking behavior and largely occur on non-overlapping populations of astroglia. Here we review the growing literature supporting a critical role for accumbens astrocytes in modulating glutamate transmission during drug seeking in rodent models of relapse.

成瘾药物的复发仍然是世界范围内的一个主要医学问题。在啮齿类动物中，伏隔核核心的谷氨酸释放会触发对压力以及与药物相关的线索和环境的反应而恢复药物寻求。成瘾中的谷氨酸失调部分是由于伏隔星形胶质细胞的长期适应造成的，包括谷氨酸转运蛋白 GLT-1 的下调以及戒断精神兴奋剂和阿片类药物后突触的回缩。虽然伏隔星形胶质细胞清除谷氨酸的能力因药物使用和戒断而受到破坏，但伏隔星形胶质细胞会经历快速、短暂的可塑性，以响应恢复寻求的药物相关线索。例如，海洛因寻求的提示恢复可通过埃兹蛋白磷酸化恢复星形胶质细胞突触的邻近性，并增强 GLT-1 表面表达。这些适应限制了药物寻求行为，并且主要发生在不重叠的星形胶质细胞群体上。在这里，我们回顾了越来越多的文献，这些文献支持伏隔星形胶质细胞在啮齿动物复发模型的药物寻找过程中调节谷氨酸传输中发挥关键作用。