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Biomedicine

Drug Erases Fearful Memories

A common drug can selectively target long-term memories better than other therapies.

A common blood-pressure drug can selectively dampen fearful memories, according to research published today in Nature Neuroscience.

The findings add support for a new approach to treating anxiety disorders: chemically blocking the emotional component of a memory as it is being recalled. In healthy volunteers, the drug was more effective than exposure therapy, one of the most common treatments for anxiety disorders, which involves repeatedly exposing patients to what they fear.

The research builds on preliminary tests in patients with post-traumatic stress disorder (PTSD), in which people who have experienced severe trauma, such as rape, are plagued by disturbing and uncontrollable memories of the event. “Anytime you can reduce the emotional component of a memory while leaving the other content intact is very exciting,” says Seth Norrholm, a neuroscientist at Emory University, in Atlanta, who was not involved in the research. “We want patients to understand what triggers their fear without feeling the anxiety.”

The findings also build on our understanding of memory, supporting the notion that even an old memory, once recalled, becomes labile and susceptible to alteration.

To create a memory, the brain moves information from short-term storage into long-term storage–a process called consolidation. Repeating a phone number soon after hearing it, for instance, uses short-term memory. But short-term memories are particularly vulnerable to interference; learning a second phone number shortly after the first is likely to wipe out the memory of the original number.

In recent years, scientists have discovered that the simple act of remembering a past experience requires that the memory be consolidated once again. And both animal research and some human studies have shown that during reconsolidation, long-term memories– once thought to be fairly stable–can be more easily meddled with.

In the new experiment, researchers from the University of Amsterdam repeatedly showed healthy volunteers pictures of spiders, one image of which was followed by an electrical shock. As the person learned to link the spider with the shock, just seeing that picture triggered anxiety. Psychologist Merel Kindt and her colleagues assessed the emotional aspect of the memory by measuring how startled a volunteer was by a loud sound accompanying the picture. This “startle response” is linked to the emotional intensity of a memory and can be measured using the movement of the eye muscles as the volunteer blinks in surprise.

The next day, scientists tested the emotional association between the electric shock and the spider by measuring the volunteers’ startle response after seeing the spider. During the tests, the researchers gave half of the group propranolol, a beta blocker that’s been used for decades to control blood pressure, and the other half a placebo. On the third day, both groups remembered the link between the shock and the spider equally well: they both accurately reported when they expected to get a shock. But those who had been treated with the drug were less startled by sound accompanying the spider, suggesting that the emotional aspect of the memory had been dampened while the informational content was left intact.

The new findings build on decades of animal research that shows that the brain stores different types of memories in different areas. A brain region called the amygdala, often dubbed the brain’s fear center, plays a central role in the storage of emotional memories. Research in animals suggests that propranolol, which blocks a certain molecule in the amygdala, interferes with reconsolidation by preventing the synthesis of proteins needed to store the memory.

Previous research has shown that propranolol can help PTSD patients. But the new study takes the work a step further, by comparing propranolol treatment with exposure therapy, commonly used with PTSD. With this treatment, patients repeatedly recall their traumatic memory in a safe environment, eventually learning to disassociate the memory from fear. “Exposure therapy is the most effective treatment for anxiety disorders,” says Kindt. “But it’s not successful for everyone, and patients relapse 20 to 60 percent of the time.”

The researchers found that after exposure therapy (also called extinction), the fearful response to the spider could be rapidly brought back. But the same was not true for those treated with propranolol, suggesting that the memory was truly weakened or erased. “It shows that blocking reconsolidation is really different than extinction, which has been a matter of controversy,” says Alain Brunet, a psychologist at McGill University, in Montreal, who has tested propranolol in PTSD patients but was not involved in the current study. Previous research suggests that exposure produces a new form of learning, rather than degrading the fearful memory. The fact that the original memory remains intact may explain the high relapse rates with this treatment, says Kindt.

Kindt’s team has already tested whether the propranolol effect lasts longer than three days–a key requirement for therapeutic use–but she declined to give the results because they have been submitted for publication. Other scientists are testing additional drugs in animals to search for potentially more potent compounds. “Whether it’s clinically going to be useful on its own, or perhaps in a cocktail of other agents that also dampen emotional state, only time will tell,” says Todd Sacktor,a neurologist and scientist at State University of New York Downstate Medical Center, in Brooklyn.

While Kindt’s study and others are promising, larger tests are required to determine how useful propranolol treatment will be, as well as the most beneficial conditions for delivery. Because the drug is widely available for other purposes, some PTSD patients have reported trying it on their own, with little success. It may be that the drug must be delivered under very controlled circumstances in order to work.

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