Elsevier Connect

Neuroscience

Drugs that weaken traumatic memories show promise for PTSD treatment

New study shows why old memories are hard to extinguish and that HDACis can facilitate psychotherapy to treat anxiety disorders

Memories of traumatic events often last a lifetime because they are so difficult to treat through behavioral approaches. A preclinical study in mice published today by Elsevier's Cell Press in the journal Cell reveals that drugs known as histone deacetylase inhibitors (HDACis) can enhance the brain's ability to permanently replace old traumatic memories with new memories, opening promising avenues for the treatment of posttraumatic stress disorder (PTSD) and other anxiety disorders.

Metabolic activity (green and red colors) in the hippocampus (white dotted line) of animals that underwent extinction training in combination with HDACis (right) is significantly higher than in animals that underwent extinction training alone (left). Metabolic activity serves to estimate the learning capacity of an animal.(Credit: Cell, Gräff et al)"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 Dr. Li-Huei Tsai, Professor of Neuroscience at 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."

One 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.

The abundance of dendrite in the hippocampus of animals that underwent extinction training in combination of HDACis (lower) is significantly higher than in animals s that underwent extinction training alone (upper). (Credit: Cell, Gräff et al)To address this question, Dr. 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 hypothesized that epigenetic modification of genes involved in learning and memory might be responsible for the diminished response of treatment for older memories.

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

"Collectively, our findings suggest that exposure-based therapy alone does not effectively weaken traumatic memories that were formed a long time ago, but that HDACis can be combined with exposure-based therapy to substantially improve treatment for the most enduring traumatic memories," Tsai said.[divider]

Read the study

Cell Press has made this study freely available on its website for two weeks, until January 30, 2014: Cell, Gräff et al: "Epigenetic priming of memory updating during reconsolidation to attenuate remote fear memories."

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Reporting for Elsevier Connect

Mary Beth O'LearyMary Beth O'Leary (@MaryBethPress) is Press Officer and Associate Media Relations Manager for Cell Press (@CellPressNews), based in Cambridge, Massachusetts. She began her career at Cell Press as an Senior Editorial Assistant for the journal Cell before transitioning into a role as Marketing/Publicity Coordinator. In December, she moved into her position as Press Officer for Cell Press's 29 journals. A graduate of the College of the Holy Cross in Worcester, Massachusetts, she studied literature and art history.



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1 Archived Comment

Billy Kobayashi January 17, 2014 at 1:44 am

This sound's very promising, however I wish that the article would elaborate on the chemical interaction/ process rather than simply presenting a conclusion that the mice have "moved past" the traumatic tone.

Does it suppress the urge to recall the traumatic experience("bypassing"/"avoiding" it) or does it remove the memory completely (memory loss) or does it alter the mice's emotional response to the memory ("acceptance").

Just my 2 cents, thank you for the article though. =)

Reply
easyzenburger February 2, 2014 at 9:32 pm

From what I've been told, (in a lecture by a neuroscientist who studies memory), it basically weakens the memory pathways. There's no way that I'm aware of to completely erase the memory, but it is slight memory loss in a sense. Memory is still an unclear phenomenon, but we know that neurons build pathways between one another when forming long term memories, and this requires proteins etc. Every time you recall something, you actually change that memory and reinforce the pathways that built it, via activating and altering the connections between neurons, adding or deleting information related to that particular memory. So, with this particular therapy, you recall the traumatic event while your brain is filled with substances that block the formation of pathways, the result being that over time the pathways that "built" the memory into existence slowly disappear. I would cite sources but that's just from what I recall from one lecture.

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