Kasten Chelsea R, Holmgren Eleanor B, Wills Tiffany A
LSU Health Sciences Center-New Orleans, Department of Cell Biology and Anatomy, Medical Education Building, 1901 Perdido Street, Room 6103, New Orleans, LA 70112, USA.
Brain Sci. 2019 Jul 30;9(8):183. doi: 10.3390/brainsci9080183.
Allosteric modulators of metabotropic glutamate 5 receptors (mGlu receptors) have been identified as a promising treatment to independently alleviate both negative affective states and ethanol-seeking and intake. However, these conditions are often comorbid and might precipitate one another. Acute and protracted ethanol withdrawal can lead to negative affective states. In turn, these states are primary drivers of alcohol relapse, particularly among women. The current review synthesizes preclinical studies that have observed the role of mGlu receptor modulation in negative affective states following ethanol exposure. The primary behavioral assays discussed are ethanol-seeking and intake, development and extinction of ethanol-associated cues and contexts, behavioral despair, and anxiety-like activity. The work done to-date supports mGlu receptor modulation as a promising target for mediating negative affective states to reduce ethanol intake or prevent relapse. Limitations in interpreting these data include the lack of models that use alcohol-dependent animals, limited use of adolescent and female subjects, and a lack of comprehensive evaluations of negative affective-like behavior.
代谢型谷氨酸5受体（mGlu受体）的变构调节剂已被确定为一种有前景的治疗方法，可独立缓解负面情绪状态以及对乙醇的寻求和摄入。然而，这些情况往往并存，且可能相互促成。急性和长期的乙醇戒断会导致负面情绪状态。反过来，这些状态是酒精复发的主要驱动因素，尤其是在女性中。本综述综合了临床前研究，这些研究观察了mGlu受体调节在乙醇暴露后负面情绪状态中的作用。所讨论的主要行为测定包括对乙醇的寻求和摄入、乙醇相关线索和环境的形成与消退、行为绝望以及类似焦虑的活动。迄今为止所做的工作支持将mGlu受体调节作为介导负面情绪状态以减少乙醇摄入或预防复发的一个有前景的靶点。解释这些数据的局限性包括缺乏使用酒精依赖动物的模型、青少年和女性受试者的使用有限，以及对类似负面情绪行为缺乏全面评估。
