Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States
Rita Baldi
Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States
Lindsay Halladay
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United States
Adrina Kocharian
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United States
Nolan Hartley
Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States
Carolyn Grace Silva
Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States
Holly Roberts
Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States
Andre Haymer
Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States
Lawrence J Marnett
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
Andrew Holmes
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United States
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
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.
