Inhibition of the COX-2 enzyme can, in a mouse model, reverse pathological anxiety behaviors induced by traumatic stress exposure, researchers at Vanderbilt University Medical Center reported this week in the journal eLife.
Sachin Patel, M.D., Ph.D., and colleagues used a chemically modified “substrate specific” COX-2 inhibitor developed at Vanderbilt called LM-4131, as well as several COX-2 inhibitors that are currently used clinically to reduce inflammation and pain.
They found that LM-4131 activates a specific type of potassium channel that reduces hyperactivity of the amygdala, a brain region involved in generating excess anxiety. LM-4131 also increases levels of endogenous cannabinoids, natural chemicals in the brain that raise mood.
The findings support development of substrate specific and possibly other COX-2 inhibitors to treat post-traumatic brain disorder (PTSD) and other stress-related psychiatric disorders like major depression.
Andrew Holmes, Ph.D., chief of the Laboratory of Behavioral and Genomic Neuroscience at the National Institute on Alcohol Abuse and Alcoholism, was the study’s co-author with Patel.
These studies were supported by grants from the National Institutes of Health (MH100096, GM015431) and by the National Institute on Alcohol Abuse and Alcoholism Intramural Research program.
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