New drugs that may treat anxiety, PTSD identified

Washington: Drugs that improve brain's ability to permanently replace old traumatic memories with new ones could help advance treatment for posttraumatic stress disorder (PTSD) and other anxiety disorders, scientists say.

Researchers in mice studies found that drugs known as histone deacetylase inhibitors (HDACis) can enhance the brain's ability to replace old traumatic memories with new memories.

"Psychotherapy is often used for treating PTSD, but it doesn't always work, especially when the traumatic events occurred many years earlier," said senior study author Li-Huei Tsai of the Massachusetts Institute of Technology.

"This study provides a mechanism explaining why old memories are difficult to extinguish and shows that HDACis can facilitate psychotherapy to treat anxiety disorders such as PTSD," Tsai said.

A common treatment for anxiety disorders is exposure-based therapy, which involves exposing patients to fear-evoking thoughts or events in a safe environment.

This process reactivates the traumatic memory, opening a short time window during which the original memory can be disrupted and replaced with new memories.

Exposure-based therapy is effective when the traumatic events occurred recently, but until now, it was not clear whether it would also be effective for older traumatic memories.

To address this question, Tsai and her team used a protocol for studying fear responses associated with traumatic memories. In the first phase, the researchers exposed mice to a tone followed by an electrical footshock.

Once the mice learned to associate these two events, they began to freeze in fear upon hearing the tone by itself, even when they did not receive a shock.

Using an extinction protocol, which is similar to exposure-based therapy, the researchers repeatedly presented the tone without the shock to test whether the mice could unlearn the association between these two events and would stop freezing in response to the tone.

The extinction protocol was successful for mice that were exposed to the tone-shock pairing just one day earlier, but it was not effective for mice that originally formed the traumatic memory one month earlier.

The researchers hypothesised that epigenetic modification of genes involved in learning and memory might be responsible for the diminished response of treatment for older memories.

Researchers tested whether HDACis, which promote long-lasting activation of genes involved in learning and memory, could replace old traumatic memories with new ones.

Mice previously exposed to the tone-shock pairing received HDACis and then underwent the extinction protocol. These mice learned to stop freezing in response to the tone, even when they originally formed the traumatic memory one month earlier.

The study is published in the journal Cell.