To test this idea, Nader conditioned rats to fear a musical tone, and when he activated the fear memory by playing the tone and the animals froze in fear, he injected anisomycin, a protein synthesis inhibitor, into their amygdalas. (The technique had previously been proven to erase new memories in rats.) In the following two hours, the rats continued to freeze when the tone was played, but 24 hours later, the tone had ceased to affect their behavior.
Nader theorized that the anisomycin had blocked the reconsolidation process, causing the memory to be lost. “What happened to it?” asks Nader. “There’s no way to know. Even if the animal never again showed fear of the tone, the memory might still be there, inaccessible but present. Clinically, though, it doesn’t matter, as long as the animal is no longer impaired.”
Although useful in investigating the possibility of reconsolidation, anisomycin isn’t a viable therapy. The drug is approved only for use in animal tests, and it blocks protein synthesis in all cells, so it would be toxic if taken systemically by animals or people. Moreover, it doesn’t just get rid of a troubling
association—the issue for people with PTSD—but also wipes out the memory itself in animals. “Having a memory vanish obviously isn’t a sound therapeutic approach in humans, because it’s our memories that define us,” says Nader. “For many patients with PTSD, their trauma is part of their identity. If they wake up one day and can’t remember what happened to them, then why were they sitting at home for the past 20 years?”
But if propranolol were given when a memory is reactivated, it might be possible to tone down the memory’s intensity while it undergoes reconsolidation. “If this is really how things work, we could have a second crack at PTSD, having patients remember the traumatic event in a controlled setting and giving them the medication and then weakening the memory,” says Pitman. “That would be a major advance.”
Pitman, Brunet, Harvard Medical School researcher Scott Orr and Nader are putting Nader’s hypothesis to the test, giving propranolol to people who have had PTSD for more than 10 years. In a pilot study of 19 people, half were given a dose of propranolol after they wrote about their trauma and half received a placebo. A week later, they returned to the lab to listen to a recording of their stories while researchers measured signs of stress and arousal. The people on the beta-blocker showed a 19% reduction in PTSD symptoms compared with an 11% decrease among those in the control group.
Although that difference appears insignificant, Brunet was heartened that there was a difference at all. “It’s pretty amazing we got such a strong result with a dose of propranolol lower than that prescribed for hypertension,” he says. “People on antidepressants have to take their meds for four to six weeks before there’s an effect.” In the current trial, following up on that pilot, subjects are asked to recall their traumatic memories and then to take propranolol once a week for six weeks. Then they’re revisited at intervals of several months so that researchers can gauge any symptoms of PTSD. The six-week regimen of treatment could tone down parts of the memory that a single dose didn’t touch, says Brunet.
“People in the pilot felt modestly better but they weren’t jumping up and saying, ‘Yahoo, let’s get out of here,’” says Nader. “But if you’ve had PTSD for 10 years, it may take a while to notice any improvement. And maybe the drug will have a bigger effect if we give it just before we trigger the memory.” Perhaps having the beta-blocker already in the body would reduce the intensity of the recalled trauma.
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