A research team led by two-time NARSAD Grantee and Foundation Scientific Council member Kerry Ressler, M.D., Ph.D., reports that a medication called osanetant, already known to be safe for use in humans, shows potential to treat the symptoms of post-traumatic stress disorder (PTSD) before they become disabling.
Dr. Ressler and colleagues at Emory University School of Medicine focused their efforts on examining the activity of a pair of genes active in the brain’s amygdala region—a region known to be involved in the processing of emotions and fear—that had been linked in earlier studies to the formation, retention and recall of traumatic memories. Traumatic memories that get retriggered persistently and cannot be “extinguished” are the primary symptom of PTSD, and can play a role in panic disorder and many phobias.
The genes in question are called Tac1 and Tac2, and while previous research studies had attempted to treat the formation of fear memories by intervening with the mechanisms set in motion by Tac1, the experiments had not proven successful in treating PTSD-like symptoms. In this new research published online June 26th in the journal Neuron, Dr. Ressler and team show promising results when focus is placed on intervening with the mechanisms set in motion by activation of the Tac2 gene.
The researchers hypothesized that interrupting Tac2 activity might be more effective in disrupting the formation and consolidation of fear memories because that gene is activated almost exclusively in brain areas that regulate the emotions (including the amygdala), whereas the Tac1 gene is activated in areas widely dispersed throughout the brain. The researchers were able to confirm that the Tac2 gene is involved in fear memory formation or “consolidation.”
Dr. Ressler, Professor of Psychiatry and Behavioral Sciences, explains that the researchers then found that “drugs that act on cells in which Tac2 is active could be used to block fear memory consolidation shortly after exposure to a trauma.” Mice given osanetant shortly after a “trauma” (a sound paired with a shock) could still learn to become afraid but the mice did not freeze as much in response to the sound a day later, even if the medication was given up to an hour after training. Osanetant is known to be safe for use in humans and further studies will now be required to determine if the desired effect is achieved and maintained in human patients.
The researchers also experimented with a methodology (using DREADD receptors) that allowed them to decrease Tac2 activity in mice; this methodology also showed reduced Tac2 activity led to impaired formation of fear memory in animal models.
These results point to new medications that could aid in preventing PTSD, Dr. Ressler says. “PTSD is unique among psychiatric disorders in that we know when it starts—at the time of the trauma. Finding ways to prevent its development in the first place—in the emergency department or the battlefield—is an important and exciting avenue of research in this area."