Researchers Prevent Onset of PTSD in Mice

Human application is about a decade away, researchers say.

Soldiers bow their heads in prayer before a deployment ceremony for another tour in 2009 at Fort Riley, Kansas. (Chris Hondros/Getty Images)

Human application is about a decade away, researchers say.

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A new drug can prevent at least some of the symptoms associated with Post Traumatic Stress Disorder in mice. Additionally, researchers believe they have pinpointed the brain receptor responsible for the fear a person suffering from PTSD feels when having an episode.

The brain receptor, called Oprl1, is also activated when a patient takes opioid drugs such as morphine or oxycodone, which could help explain why previous studies have suggested that morphine administered immediately after a traumatic event may help ease anxiety felt by PTSD patients. PTSD is often characterized as the "persistent re-experiencing of a traumatic event," which can often include flashbacks and nightmares.

According to the National Institutes of Health, PTSD affects about 7.7 million American adults. That number has increased in recent years due to veterans returning home from wars in Afghanistan and Iraq. Though PTSD is poorly understood, Kerry Ressler, an Emory University professor and lead author of Wednesday's study, published in Science Translational Medicine, says it's one neurological disorder whose riddle may soon be solved.

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"It's a complex problem, but we think it might be one of the most tractable neurological disorders because we know the disorder starts because of a trauma," Ressler says. "It's complex, but we have this temporal component to it that we don't have with other disorders."

That means it's also relatively easy to induce a PTSD-like scenario in mice. Ressler and his colleagues were able to condition mice to fear a certain audible tone by administering an electrical shock anytime it was played. The next day, the same sound was played without the shock. Mice that had not been treated with a drug they developed froze in place, demonstrating fear. Mice that had been given an injection of the drug, which activates the Oprl1 receptor, showed much less fear. Mice given the drug did not exhibit any obvious side effects.

"This drug binds to that receptor, by doing that, it decreases the fear memory in the mice," says Raul Andero, who worked with Ressler on the study. The drug was effective whether it was injected into the brain or the abdomen, and was effective when injected either before or within 48 hours of the traumatic event.

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Though it's impossible to know whether the mice are experiencing "true" PTSD, because as Andero says, "you can't ask a mouse if they have PTSD" or are experiencing nightmares or flashbacks, Ressler says the team can be sure they are at least experiencing the fear associated with PTSD.

"We have a model of mice fear that is a good model of human fear. We have confidence that we're looking at the same thing," Ressler says.

Andero says that, in a way, it prevents the mice from ever forming a fearful memory associated with the traumatic event. But the drug is associated with the "emotional" memory, not the static memory itself, so if administered to a soldier, they presumably wouldn't completely forget the actions that led to the trauma.

"The mice remember that the tone was dangerous but not as much as the animals that didn't get the drug," Andero says. "We're trying to block the emotions associated with remembering. Ideally, this blockade of the memory wouldn't make them completely forget what happened."

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Though popular in movies such as "Eternal Sunshine of the Spotless Mind" and "Paycheck," completely forgetting events would cause major ethical issues, Ressler says. The team plans on moving on from mice to slightly larger animals before eventually testing the drug on humans in small doses. They won't know whether memories are truly forgotten until human trials.

"Given these trials, we'd expect it only to lessen the fear," Ressler says. "Ethically, people don't want to create a full amnesia for a whole lot of reasons. We want to find a way to target the emotional memory but not the declarative part."