Endocannabinoid signalling modulates susceptibility to traumatic stress exposure.

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
Nat Commun. 2017 8: 14782

PMID: 28348378 · PMCID: PMC5379055 · 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.

MeSH Terms (24)

Amygdala Animals Anxiety Arachidonic Acids Behavior, Animal Benzodioxoles Disease Susceptibility Dronabinol Endocannabinoids Excitatory Postsynaptic Potentials Female Glutamates Glycerides Hippocampus Lipoprotein Lipase Male Mice, Inbred ICR Mice, Knockout Phenotype Piperidines Resilience, Psychological Signal Transduction Stress, Psychological Synapses

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