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Cyclooxygenase-2 inhibition reduces stress-induced affective pathology

2016; eLife Sciences Publications Ltd; Volume: 5; Linguagem: Inglês

10.7554/elife.14137

2050-084X

Joyonna Gamble‐George, Rita Báldi, Lindsay R. Halladay, Adrina Kocharian, Nolan D. Hartley, Carolyn Grace Silva, Holly Roberts, Andre Haymer, Lawrence J. Marnett, Andrew Holmes, Sachin Patel,

Neuroendocrine regulation and behavior

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.