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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Metabotropic and ionotropic glutamate receptors as neurobiological targets in anxiety and stress-related disorders: Focus on pharmacology and preclinical translational models
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Metabotropic and ionotropic glutamate receptors as neurobiological targets in anxiety and stress-related disorders: Focus on pharmacology and preclinical translational models

机译：代谢型和离子型谷氨酸受体作为焦虑症和应激相关疾病的神经生物学靶标：专注于药理学和临床前转化模型

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摘要

Anxiety disorders are amongst the most common and disabling of psychiatric illnesses and have severe health and socio-economic implications. Despite the availability of a number of treatment options there is still a strong medical need for novel and improved pharmacological approaches in treating these disorders. New developments at the forefront of preclinical research have begun to identify the therapeutic potential of molecular entities integral to the biological response to adversity, particularly molecules and processes that may pre-determine vulnerability or resilience, and those that may act to switch off or "unlearn" a response to an aversive event. The glutamate system is an interesting target in this respect, especially given the impact anxiety disorders have on neuroplasticity, cognition and affective function. These areas of research demonstrate expanding and improved evidence-based options for treating disorders where stress in various guises plays an important etiological role. The current review will discuss how these pathways are involved in fear circuitry of the brain and compare the strength of therapeutic rationale as well as progress towards pharmacological validation of the glutamate pathway towards the treatment of anxiety disorders, with a particular focus on metabotropic and ionotropic glutamate receptors. Specific reference to their anxiolytic actions and efficacy in translational disease models of posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder and phobia will be made. In addition, the availability of ligands necessary to assist clinical proof of concept studies will be discussed.
机译：焦虑症是最常见的精神病患者之一，具有严重的健康和社会经济影响。尽管有许多治疗选择可用，但仍强烈需要用于治疗这些疾病的新颖和改良药理学方法的医学需求。临床前研究前沿的新发展已开始确定与生物对逆境的反应不可或缺的分子实体的治疗潜力，特别是可能预先确定脆弱性或适应力的分子和过程，以及可能起到关闭或“学习性作用”的分子和过程。对厌恶事件的回应。在这方面，谷氨酸系统是一个有趣的目标，特别是考虑到焦虑症对神经可塑性，认知和情感功能的影响。这些研究领域证明了扩大和改进的以证据为基础的治疗疾病的选择，这些疾病在各种形式的压力中起着重要的病因作用。本篇综述将讨论这些途径如何参与大脑的恐惧回路，并比较治疗基本原理的强度以及朝着治疗焦虑症的谷氨酸途径的药理学验证的进展，特别着重于代谢型和离子型谷氨酸受体。将具体参考它们在创伤后应激障碍，强迫症，惊恐症和恐惧症等转化性疾病模型中的抗焦虑作用和功效。另外，将讨论辅助临床概念验证研究所必需的配体的可用性。

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