The endocannabinoid system and anxiety responses
The endocannabinoid system and anxiety responses
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DOI：
10.1016/s1569-7339(07)00014-8
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Piomelli, Daniele
中科院分区：
文献类型：
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作者：
Bortolato, Marco;Piomelli, Daniele
作为大麻的主要精神活性成分，德尔塔(9)-四氢大麻酚（THC）对人类和实验动物的情绪状态产生复杂的调节作用。四氢大麻酚（THC）及其内源性配体（内源性大麻素（endocannabinoids））激活的受体的表征已经启动了许多研究，探索内源性大麻素系统的功能及其对焦虑相关和情绪反应的影响。选择性药理学工具和基因工程小鼠的发展促进了这些研究，使人们认识到内源性大麻素系统在调节情绪状态中起着重要作用。然而，它对焦虑相关行为的影响是高度可变的，可能取决于不同受体、大脑区域和神经递质系统的参与。此外，许多因素有助于调节内源性大麻素对焦虑的作用，如遗传背景，年龄，性别和情境背景。在特定的环境条件下，内源性大麻素信号的药理增强确实被证明在啮齿动物中产生类似焦虑和情绪增强的功能，而不会引起四氢大麻酚和其他大麻素激动剂引起的广泛的不良行为反应。因此，内源性大麻素系统可能是抗焦虑治疗的一个新的药理靶点。在这里，我们对内源性大麻素系统参与焦虑相关反应的现状进行了全面的概述，并强调了目前该领域研究的挑战以及该系统在焦虑障碍治疗中提供的新视角。
The main psychoactive ingredient of Cannabis sativa, Delta(9)-tetrahydrocannabinol (THC) produces complex modulatory effects on emotional states in humans and laboratory animals. The characterization of the receptors activated by THC and their endogenous ligands (endocannabinoids) has initiated numerous studies exploring the functions of the endocannabinoid system and its impact on anxiety-related and emotional responses. These studies, which have been facilitated by the development of selective pharmacological tools and genetically engineered mice, have led to recognize that the endocannabinoid system plays an important role in the regulation of emotional states. However, its impact on anxiety-related behaviors is highly variable, probably depending on the involvement of different receptors, brain regions and neurotransmitter systems. Furthermore, numerous factors contribute to modulate the role of endocannabinoids on anxiety, such as genetic background, age, sex and situational context. Under specific environmental circumstances, pharmacological enhancement of endocannabinoid signaling has indeed been shown to produce anxiolytic-like and mood-enhancing functions in rodents, without causing the wide spectrum of untoward behavioral responses induced by THC and other cannabinoid agonists. Thus, endocannabinoid system might be a novel pharmacological target for anti-anxiety therapy. Here we provide a comprehensive overview on the current state of knowledge of the involvement of endocannabinoid system in anxiety-related responses and highlight the present challenges of research in this field as well as the novel perspectives offered by this system in the therapy of anxiety disorders.