Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
The Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Nat Commun. 2017 Mar 28;8:14782. doi: 10.1038/ncomms14782.
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.
压力是加剧和发展情感障碍（包括重度抑郁症和创伤后应激障碍）的普遍危险因素。了解赋予对压力不利后果的适应能力的神经生物学机制，可能对治疗和预防情绪和焦虑障碍具有广泛的意义。我们利用实验室小鼠及其对压力的先天个体间差异，证明了内源性大麻素 2-花生四烯酸甘油（2-AG）在压力适应中的关键作用。具体来说，系统 2-AG 增强与压力适应表型相关，并增强先前易感小鼠的适应能力，而系统 2-AG 耗竭或 CB1 受体阻断增加先前适应小鼠的易感性。此外，压力适应与腹侧海马-杏仁核谷氨酸能突触中相位 2-AG 介导的突触抑制增加有关，而杏仁核特异性 2-AG 耗竭会损害对重复应激的成功适应。这些数据表明，杏仁核 2-AG 信号机制促进对急性创伤性应激的不利影响的适应能力，并促进对重复应激暴露的适应。
