title: Cyclooxygenase-2 inhibition reduces stress-induced affective pathology.
abstract: Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show that traditional COX-2 inhibitors and a newly developed substrate-selective COX-2 inhibitor (SSCI) reduce a variety of stress-induced behavioral pathologies in mice. We found that these behavioral effects were associated with a dampening of neuronal excitability in the basolateral amygdala (BLA) ex vivo and in vivo, and were mediated by small-conductance calcium-activated potassium (SK) channel and CB1 cannabinoid receptor activation. Taken together, these data provide further support for the potential utility of SSCIs, as well as traditional COX-2 inhibitors, as novel treatment approaches for stress-related psychiatric disorders.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States.|Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States.
authors.forename: Joyonna Carrie
authors.identifier: 0000-0002-5492-9216
authors.initials: JC
authors.lastname: Gamble-George
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States.
authors.forename: Rita
authors.initials: R
authors.lastname: Baldi
authors.affiliation: Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United States.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Halladay
authors.affiliation: Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United States.
authors.forename: Adrina
authors.initials: A
authors.lastname: Kocharian
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States.|Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States.
authors.forename: Nolan
authors.initials: N
authors.lastname: Hartley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States.
authors.forename: Carolyn Grace
authors.initials: CG
authors.lastname: Silva
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States.
authors.forename: Holly
authors.initials: H
authors.lastname: Roberts
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States.
authors.forename: Andre
authors.initials: A
authors.lastname: Haymer
authors.affiliation: A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, and Vanderbilt-Ingram Cancer Center, Nashville, United States.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.affiliation: Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Holmes
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States.|Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States.|Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, United States.|Vanderbilt Kennedy Center for Human Development, Vanderbilt University Medical Center, Nashville, United States.
authors.forename: Sachin
authors.identifier: 0000-0001-8052-520X
authors.initials: S
authors.lastname: Patel
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D051379:Mice; D013312:Stress, Physiological / Q000187:drug effects*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: COX-2; PTSD; amygdala; anxiety; cannabinoid; mouse; neuroscience; stress