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The theory of reconsolidation: Memories are encoded at a cellular level as a complex set of connections between neurons. When an animal learns, for example, that a certain sound signals a food reward, new neural connections are made to solidify the memory. However, even stable memories can be vulnerable to erasure under certain circumstances. The theory of reconsolidation attempts to explain why.

A pilot study of the treatment found that propranolol did seem to soothe the anxiety provoked by patients’ traumatic memories, long after the drug itself was gone from the body. In the study, patients wrote down their recollections of the trauma and then took a single dose of propranolol or a placebo. Those who received the drug were much calmer–as measured by heart rate and skin conductance–when reading a script of their stories a week later.

A larger study of about 60 people is now almost complete. Preliminary findings show a 40 to 50 percent improvement in self-reported symptoms among those taking the drug. At the end of the trial, nearly two-thirds of the patients in one of the groups taking propranolol no longer met the criteria for PTSD. The same was true for less than 10 percent of control patients.

Brunet pulls up a graph on his computer screen, its downward-slanting line reflecting the continued decline in the propranolol recipients’ PTSD symptoms over the five weeks of the study. “We’re seeing at least as good, if not better, results than people get with exposure treatment–and in much less time,” he says. (In exposure treatment, one of the most common types of behavioral therapy for PTSD, patients repeatedly recall the details of their trauma with a therapist in a safe environment, eventually learning to dissociate the extreme fear from the details of the event.) And patients were still doing well four months after treatment, even though relapse is fairly common in PTSD therapy.

Though the results are preliminary (the treatment must still be tested in a proper double-blind study, in which neither patients nor physicians know who is getting the drug rather than the placebo), the work has attracted great interest. The U.S. Department of Defense has awarded Brunet, Pitman, and Nader a $7 million grant over four years to identify additional existing drugs that can target reconsolidation more effectively than propranolol. The study will focus on drugs that are already on the market, which means they are already deemed safe and can be tested in PTSD patients without additional animal testing. Pitman and his colleagues are currently testing opioids such as morphine in rodents. His group has also seen preliminary success in rodents with RU-486, the abortion pill; in addition to affecting progesterone, a hormone involved in pregnancy, the drug blocks the action of chemicals called glucocorticoids, which are found in the amygdala and play a role in the emotional aspect of memories.

Thumbing through a thick stack of grant applications on his desk, Brunet says he thinks that targeting reconsolidation will alleviate a range of problems beyond PTSD. “We might have discovered a new way of treating mental disorders,” he says. “There are several disorders that have at their core a problem with emotional memories.” Specifically, he says, “many types of addictions, while physiological, also include a psychological component.”

While the role of memory may not be an obvious consideration in treating drug abuse, the sights, sounds, and smells that remind addicts of their habit are a strong trigger for relapse. Brain imaging studies demonstrate that if an addict is shown a trigger, such as a needle, the part of the brain associated with drug use immediately fires up. Psychiatrists have tried exposure therapy to rid addicts of these intrusive memories, with little success. However, studies show that blocking the reconsolidation of drug-linked memories works remarkably well in animals. In fact, says Barry Everitt, a neuroscientist at the University of Cambridge in England, “it’s the only thing that works well.”

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Credits: Gérard dubois, Bryan Christie Design
Video by Emily Singer

Tagged: Biomedicine

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