Drug Helps Mice Respond Normally to Fear After Traumatic Experience

Kerry J. Ressler, M.D., Ph.D. - Brain & Behavior research expert on ptsd
Kerry J. Ressler, M.D., Ph.D.

In treating post-traumatic stress disorder (PTSD), the goal is to find ways to help patients “extinguish” abnormal and exaggerated fear responses that can continue long after a traumatic event. In a new study with mice, Foundation Scientific Council member Kerry J. Ressler, M.D., Ph.D., and his colleagues show that treatment with the corticosteroid drug dexamethasone can help the animals lose their PTSD-related fear response, possibly through the drug’s effects on a gene called Fkbp5.

The findings, published online July 15 in the journal Neuropsychopharmacology, could help the researchers learn more about the underlying genetics of PTSD, and may reveal  an opportunity to halt the disorder soon after people experience a traumatic event. Dr. Ressler, of Emory University, who in 2002 and 2005 received NARSAD Young Investigator awards, was joined on the study by 2013 Young Investigator Torsten Klengel, M.D.; 2008 Young Investigator Seth D. Norrholm, Ph.D.; 2014 Young Investigator Raül Andero Galí, Ph.D.; and 2010 Young Investigator and 2015 NARSAD Independent Investigator Tanja Jovanovic, Ph.D.

The researchers trained a group of mice using sounds and mild electrical shocks to learn and then to inhibit a specific fear. Animals that had experienced a traumatic event before the fear training were more likely to inhibit or extinguish the fear if they were given a low dose of dexamethasone four hours beforehand to suppress the internal stress response. The fear was also more likely to remain “extinguished” 24 hours later in those same animals.

Dr. Ressler and colleagues also showed that the dexamethasone dose affected how a gene called Fkbp5 is expressed in the amygdala, a part of the brain involved in regulating fear and anxiety. They suggest that dexamethasone may help to extinguish fear learning after a trauma through its effects on Fkbp5, specifically in that gene’s role in helping regulate the response to stress.

The study adds to the body of research implicating Fkbp5 in PTSD, including earlier reports by Dr. Ressler and others that have indicated certain mutations in the gene may be related to whether childhood victims of trauma grow up to develop PTSD as adults, for instance.

Read the abstract.

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