Endocannabinoid signalling modulates susceptibility to traumatic stress exposure.
Endocannabinoid signalling modulates susceptibility to traumatic stress exposure.
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DOI：
10.1038/ncomms14782
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发表时间：
2017-03-28
影响因子：
16.6
通讯作者：
Patel S
中科院分区：
文献类型：
--
作者：
Bluett RJ;Báldi R;Haymer A;Gaulden AD;Hartley ND;Parrish WP;Baechle J;Marcus DJ;Mardam-Bey R;Shonesy BC;Uddin MJ;Marnett LJ;Mackie K;Colbran RJ;Winder DG;Patel S
压力是情感性精神障碍（包括重性抑郁症和创伤后应激障碍）恶化和发展的普遍危险因素。了解神经生物学机制赋予弹性的负面后果的压力可能有广泛的意义，治疗和预防情绪和焦虑症。我们利用实验室小鼠和它们在应激易感性方面的先天个体间差异来证明内源性大麻素2-花生四烯酰甘油（2-AG）在应激恢复中的关键作用。具体而言，全身性2-AG增强与应激弹性表型相关，并增强先前易感小鼠的弹性，而全身性2-AG耗竭或CB 1受体阻断增加先前有弹性小鼠的易感性。此外，压力恢复力与腹侧海马-杏仁核神经元能突触的阶段性2-AG介导的突触抑制增加有关，杏仁核特异性2-AG耗竭损害对重复压力的成功适应。这些数据表明，杏仁核2-AG信号机制促进恢复急性创伤应激的不利影响，并促进适应反复的压力暴露。了解压力易感性的个体间差异可能会导致新的治疗和预防策略的压力相关的病理。在这里，作者提供的证据表明，增加内源性大麻素信号是一种弹性因素，可以缓冲压力的不利后果。
Stress is a ubiquitous risk factor for the exacerbation and development of affective disorders including major depression and posttraumatic stress disorder. Understanding the neurobiological mechanisms conferring resilience to the adverse consequences of stress could have broad implications for the treatment and prevention of mood and anxiety disorders. We utilize laboratory mice and their innate inter-individual differences in stress-susceptibility to demonstrate a critical role for the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) in stress-resilience. Specifically, systemic 2-AG augmentation is associated with a stress-resilient phenotype and enhances resilience in previously susceptible mice, while systemic 2-AG depletion or CB1 receptor blockade increases susceptibility in previously resilient mice. Moreover, stress-resilience is associated with increased phasic 2-AG-mediated synaptic suppression at ventral hippocampal-amygdala glutamatergic synapses and amygdala-specific 2-AG depletion impairs successful adaptation to repeated stress. These data indicate amygdala 2-AG signalling mechanisms promote resilience to adverse effects of acute traumatic stress and facilitate adaptation to repeated stress exposure. Understanding inter-individual differences in stress-susceptibility could lead to novel treatments and preventative strategies for stress-related pathologies. Here the authors provide evidence that increased endocannabinoid signalling is a resilience factor that buffers against adverse consequences of stress.