Nat Commun. 2017 Mar 28;8:14782. doi: 10.1038/ncomms14782.
Bluett RJ1,2, Báldi R1, Haymer A1, Gaulden AD1, Hartley ND1,2, Parrish WP3, Baechle J1, Marcus DJ1,2, Mardam-Bey R1, Shonesy BC3, Uddin MJ4, Marnett LJ4,5, Mackie K6, Colbran RJ2,3,7,8, Winder DG1,2,3,7,8, Patel S1,2,3,7,8.
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.