Cyclooxygenase-2 inhibition reduces stress-induced affective pathology

Joyonna Carrie Gamble-George, Rita Baldi, Lindsay Halladay, Adrina Kocharian, Nolan Hartley, Carolyngrace Silva, Holly Roberts, Andre Haymer, Lawrence J. Marnett, Andrew Holmes, Sachin Patel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Article numbere14137
JournaleLife
Volume5
Issue numberMAY2016
DOIs
StatePublished - May 10 2016
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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