Fear Erased in Rat Brains

Andrea Thompson

Date: 02 April 2009 Time: 10:04 AM ET

Fearful memories have a powerful grip on the brain, but researchers have developed a new technique in rats that loosens that grip and overwrites the fear response permanently.

The technique, involving exposing rats to the very thing they were primed to fear and taking advantage of a moment of weakness in memory of that fear, could eventually be used to develop clinical treatments of fears in humans, the scientists said.

Fear memories, like other bad memories, are particularly sticky in the brain compared to "good" ones. Evolution played a hand in this, the thinking goes, because fearing things that can harm us is an advantage to survival.

So the brain has a hard time letting go of these memories, as well as distinguishing rational from irrational fears. Researchers have long looked for a way to short-circuit the brain and help it delete those irrational fears.

Formation of a fear

A fearful memory is of course triggered by some stimulus or event that scares us, say a dog bite that causes a fear of dogs. That memory doesn't get lodged into the brain right away though.

"Initially the memory is sort of weak and it can be easily disrupted at that point," said study leader Marie-H. Monfils of the University of Texas in Austin. But given enough time, that memory becomes ingrained and stored into long-term memory, "and then it's super hard to go and disrupt," Monfils explained.

Any time we come into contact with the stimulus that prompted the fear — in this example, a dog — the memory comes out of storage and triggers our fear response.

Previous studies found that when this memory was retrieved, though, it becomes weak again as it was when it first formed. "It's almost like it makes the memory young again," Monfils told LiveScience.

Eventually the memory reconsolidates and is put back in storage in long-term memory, but this process takes some time, so during reconsolidation, the memory is "basically open to disruption," Monfils explained.

Scientists have tried to devise ways to take advantaged of this window of opportunity to either block the reconsolidation or weaken the connection between the stimulus and the fearful response.

Window of opportunity

Some groups have looked to different drugs to biochemically block the process, and while some drugs work, many can't be used in humans. One recent study though did find that common blood pressure medicine seemed to erase the fearful memory. But other studies with the drug didn't show the same positive effects, prompting Monfils and her colleagues to look for a way to block reconsolidation behaviorally.

They combined this blocking with another commonly tried technique called extinction. Their work, detailed in the April 3 issue of the journal Science, was funded in part by the National Institutes of Health.

This method as used in lab rats involves inducing a fear of a certain tone by pairing a shock with the tone. Then the tone is sounded repeatedly on its own without the shock, "until the animal no longer shows a fear response," Monfils said.

The problem with this technique is that after a time, "their fear comes right back," she added.

(The same technique is used in clinical settings where it is called exposure therapy. If you have a fear of spiders for example, you will gradually be exposed to them until your fearful reaction stops. But the same relapse to fear can happen.)

Monfils and her colleagues were looking for something more permanent. They wanted to "combine the strength of both of these techniques," she said.

A permanent solution

They used the same tone/shock pairing to induce a fear response in rats. The tone was then sounded just once without the shock, which opened up the fearful memory, but created a new "path" in the brain that indicated that the shock wasn't something to fear. After a waiting period, the tone would then be sounded repeatedly as in the normal extinction method.

This seemed to rid the rats of their fear of the tone, and when tested a month later, there was no relapse.

The key difference was opening up the memory before trying the extinction technique, Monfils explained. Regular extinction opens both the normal fearful association and the new benign association. Monfils' method has just one path, the benign one. That path is reinforced during extinction, effectively permanently overwriting the fearful memory, Monfils and her colleagues concluded.

The technique is a long way from being applied to humans in clinical situations, but Monfils is optimistic and she and her team have taken the first steps by trying to replicate the rat experiment in humans.

"I think things are really promising," she said.