title: Endocannabinoid signalling modulates susceptibility to traumatic stress exposure.
abstract: 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.
authors.affiliation: 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.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Bluett
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Báldi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Haymer
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Gaulden
authors.affiliation: 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.
authors.forename: Nolan D
authors.initials: ND
authors.lastname: Hartley
authors.affiliation: Department of Molecular Physiology &Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Walker P
authors.initials: WP
authors.lastname: Parrish
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Baechle
authors.affiliation: 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.
authors.forename: David J
authors.initials: DJ
authors.lastname: Marcus
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Mardam-Bey
authors.affiliation: Department of Molecular Physiology &Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Shonesy
authors.affiliation: A.B. Hancock Jr. Memorial Laboratory for Cancer Research and Vanderbilt Institute of Chemical Biology, Nashville, Tennessee 37232, USA.
authors.forename: Md Jashim
authors.initials: MJ
authors.lastname: Uddin
authors.affiliation: A.B. Hancock Jr. Memorial Laboratory for Cancer Research and Vanderbilt Institute of Chemical Biology, Nashville, Tennessee 37232, USA.|Departments of Biochemistry, Chemistry and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.affiliation: The Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.|Department of Molecular Physiology &Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.|Vanderbilt Kennedy Center for Human Development, Nashville, Tennessee 37232, USA.|Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Roger J
authors.identifier: 0000-0001-7401-8244
authors.initials: RJ
authors.lastname: Colbran
authors.affiliation: 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.|Department of Molecular Physiology &Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.|Vanderbilt Kennedy Center for Human Development, Nashville, Tennessee 37232, USA.|Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Danny G
authors.initials: DG
authors.lastname: Winder
authors.affiliation: 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.|Department of Molecular Physiology &Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.|Vanderbilt Kennedy Center for Human Development, Nashville, Tennessee 37232, USA.|Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Patel
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000523:psychology; D001095:Arachidonic Acids / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D052117:Benzodioxoles / Q000494:pharmacology; D004198:Disease Susceptibility; D013759:Dronabinol / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005971:Glutamates / Q000378:metabolism; D005989:Glycerides / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D010641:Phenotype; D010880:Piperidines / Q000494:pharmacology; D055500:Resilience, Psychological / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D052117:Benzodioxoles; D063388:Endocannabinoids; D005971:Glutamates; D005989:Glycerides; C534333:JZL 184; D010880:Piperidines; D013759:Dronabinol; C094503:glyceryl 2-arachidonate; D008071:Lipoprotein Lipase