To Pluck a Rooted Sorrow

Nader injected a drug that stops protein synthesis into the rat's amygdala. These inhibitors have been used for decades in memory research, but Nader was testing the technique in a new way. His hypothesis was that if he could block reconsolidation of the rat's original fearful memory, it would no longer freeze. When he played the tone and gave the drug a day later and even 14 days later, the rats were indeed blasé about the whole ordeal. That memory linking sound and fear, which was supposed to be immutable, was now defunct. "I went, 'holy cow'," Nader says. " 'This is insane!' "

Researchers first proposed reconsolidation in the late 1960s, but it never caught on. Now science was showing it might be real, and Pitman, who sees the ravages of PTSD in his patients, wanted to get into the act. Already, Pitman had conducted a study in accident victims to see if propranolol, a drug that reduces anxiety, could stop long-term traumatic memories from forming in the first place. Propranolol blocks the action of adrenaline—a stress hormone known to strengthen an emotionally significant memory—and McGaugh had previously shown that the drug could weaken memories in rats. But the approach had two major drawbacks in humans: not everybody who goes through a wrenching ordeal develops PTSD, and nobody wants to medicate unnecessarily. And because memories can consolidate from short term to long term in a matter of hours, patients might get the drug too late. Reconsolidation offered a new line of attack. "If it's true that reactivating memory returns it to an unstable state, here we have a golden second chance," says Pitman. "The implications for PTSD are huge."

Pitman teamed up with Nader, now a neuroscientist at McGill University, and Alain Brunet, a McGill psychologist. The team tested a single dose of propranolol in patients with PTSD. Participants did do better, but most still reported feeling upset by their trauma. Now researchers are giving multiple doses to see if they can get an even stronger effect. "The idea is that over time, we will chip away at this memory," says Pitman. Joël Coutu, 43, signed up for a trial conducted by Brunet. Twelve years ago, two men robbed the pet-food store where Coutu was manager, put a gun to his head and threatened to kill him. Coutu played dead after one of the criminals bashed his head with the weapon. For years, he had nightmares and flashbacks. He broke up with his girlfriend; he quit a job he loved as president of a bird club in Montreal. Usually upbeat, Coutu became depressed. "Inside, I was dying," he says.

On his first visit with Brunet, Coutu wrote down the details of his trauma. Once a week for six weeks after that, he received propranolol, then read the disturbing account. At first, it was agony. "I realized all these emotions I thought were gone weren't," he says. But the fifth time, Coutu noticed a distinct change. "I felt like smiling. All of a sudden, it wasn't me anymore." At his last session, doctors tested Coutu's physiological reactions—his heartbeat, his palm sweat, his facial muscles—to his script and to neutral stories, like a beach scene. His response was similar. "It feels like there's been water poured on the fire," he says. Brunet's early data are compelling: participants' symptoms dropped by 50 percent, and 70 to 80 percent no longer meet the full criteria for PTSD.

What's so fascinating about this research is how it plays on the geography of memory. We often think of memory as one entity wrapped neatly in a bow. But our remembrance of a single experience lands like confetti in the brain, scattered into different locations. The dry facts about what happened—I was walking home, a man assaulted me—appear to lodge in the hippocampus. But the emotional trauma of that same event—the anger at the man, the horror of the moment—seem to be housed in the amygdala. When the memory is recalled, both parts emerge together, like the sound and images in a movie, says Brunet. This is critical to the science of forgetting: researchers believe they may be able to target the fear part of the memory but leave the details of what happened intact. "People cherish their memories, even their bad memories," says Brunet. "They don't want them to be erased, they want to recall them with less pain."

Will memory eradication become all the rage? "I get calls from patients weekly wanting to erase their traumatic memories," says LeDoux. "One guy wants to get rid of the memory of his ex-wife." That will almost certainly never happen. But improving treatment for PTSD and other conditions (researchers are targeting the "appetitive" memory in addicts) is a laudable goal. Not every memory can be reconsolidated, however, and no one's sure that propranolol will be the best therapy. Pitman is studying other medications, too, including a painkiller, a nausea drug and RU-486 (the abortion pill).

Is all of this ethical? Is it real? Kandel says science must always move forward, but, he adds, "removing memory gets into dangerous territory. We have to think about it very carefully." McGaugh, citing conflicting data, doesn't even buy the theory of reconsolidation, though he admits to being in the minority.