Home' Technology Review : May June 2009 Contents FEATURE STORY 59
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A larger study of about 60 people is now almost complete. Pre-
liminary 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 dis-
sociate 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 e ectively 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 test-
ing. 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 a ecting proges-
terone, 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 alle-
viate a range of problems beyond PTSD. "We might have discov-
ered 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. Psy-
chiatrists 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."
Easing the pain of di cult memories sounds like a dream come
true, perhaps even for people who don't su er from anxiety disor-
ders. But the idea also raises concerns. Such memories, after all, are
an integral part of a person: frightening, sad, perhaps life-changing
moments make up important chapters in the stories of our lives.
We might not be the same if remembering these events felt no more
emotional than recalling a trip to the grocery store.
But Brunet points out that he is trying to bring PTSD patients'
memories into a normal emotional range, not blunt their power
altogether. "Months after a breakup, when the pain is beginning
to fade away, do you feel that you have lost something?" he asks.
"Of course not. That's the fate of normal emotional memory." In
PTSD, on the other hand, the memory is as painful and crippling
as if the events had occurred yesterday, making it di cult to lead
a normal life. He doesn't think that using propranolol to render
these memories bearable would create any unique potential for
abuse as a way to dull the regrets, fears, and embarrassments
of everyday life; people already use alcohol and other drugs for
The ethical worries may stem in part from a misunderstanding
about the level of control that scientists have over memory. Research-
ers can manipulate memories only in very subtle ways. It's not possi-
ble to erase a web of interconnected memories, or to program people
with substantial new memories. (Research into false memories and
eyewitness testimony suggests that a memory can be subtly influ-
enced: someone who has witnessed a car accident, for example, may
estimate di erent speeds for the car depending on whether they are
asked how fast they saw it "smash" or "bump" into a tree. But these
changes are minor tweaks to existing memories.)
It's still too early to predict the ultimate impact that drugs and other
treatments targeting reconsolidation will have on human memory.
But for now, the power to block reconsolidation is giving scientists a
new tool to probe the brain's storage system. Nader's next step is to use
his research on reconsolidation to study how the brain files memories.
If rats are taught two di erent associations---say, pairing a light with a
shock and a sound with a shock---does blocking the reconsolidation
of one memory a ect the other? Experiments like this will begin to
shed light on whether memories are stored according to when they
were formed, the context in which they were formed, or other vari-
ables. Bit by bit, the answers to such questions should help unravel
one of the most enticing mysteries of the mind.
EMILY SINGER IS TECHNOLOGY REVIEW'S SENIOR EDITOR FOR BIOMEDICINE.
Karim Nader discusses memory manipulation in a video interview:
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