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.

吸毒成瘾的复发仍然是世界范围内的主要医学问题。在啮齿动物中，伏隔核核心中的谷氨酸释放触发恢复药物寻求以响应压力，以及与药物相关的线索和环境。成瘾中的谷氨酸能失调部分是由于伏隔核星形胶质细胞的长期适应，包括谷氨酸转运蛋白 GLT-1 的下调和从精神兴奋剂和阿片类药物戒断后突触的收缩。虽然它们清除谷氨酸的能力因药物使用和戒断而受到破坏，但伏隔核星形胶质细胞在响应恢复寻求的药物相关线索时经历快速、短暂的可塑性。例如，海洛因寻求线索的恢复通过埃兹蛋白磷酸化恢复星形胶质细胞突触的接近性，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中。在这里，我们回顾了越来越多的文献，这些文献支持伏隔核星形胶质细胞在啮齿动物复发模型中在寻找药物期间调节谷氨酸传递中的关键作用。