To use reconsolidation to wipe out drug memories — and consequently, craving — Dr. Yan-Xue and his team first taught rats to self-administer cocaine and heroin. The rats quickly learned to associate a particular environment with a drug high.
The Peking University investigators then put the rats in the same environment — but didn’t make the drugs available. They found that “the rats showed the least drug-seeking behavior if they were put in the drug-taking environment for 15 minutes, removed from it for 10 minutes, and then returned for three hours,” Costandi reports in Nature.
“Next, the researchers applied the procedure to humans,” Costandi writes, on 22 heroin addicts who had been ‘clean’ for an average of 11 years and who had taken part in the study.
Former addicts were grouped into three. Those in one “treatment” groups were shown a brief video to remind them of taking drugs — opening the ‘memory window.’ Those in the “control” group were shown an initial video of the countryside, which would not open the window. Ten minutes later, both groups were made to watch more videos and look at pictures of heroin drug use. The third group — also a treatment group — was also made to watch more videos and look at pictures of heroin drug use.
Lu, one of the researchers, reports that addicts who were shown the video 10 minutes before the ‘extinction’ session showed decreased drug cravings both during the session — and even up to six months later. Those who watched the video six hours before the session, didn’t enjoy reduced cravings.
“Neuroscientists think that the brief exposure beforehand reactivates the memory of drug taking, making it easier to erase the link between the cues of drug taking and getting high, and to replace it with a memory in which no such link is formed,” journalist Costandi writes.
“Drug use and relapse involve learned associations between drug-associated environmental cues and drug effects. Extinction procedures in the clinic can suppress conditioned responses to drug cues, but the extinguished responses typically reemerge after exposure to the drug itself (reinstatement), the drug-associated environment (renewal), or the passage of time (spontaneous recovery),” the investigators write in their paper in Science.
“In heroin addicts, retrieval of drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin craving 1, 30, and 180 days later,” he says. “The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing drug craving and relapse during abstinence,” the researchers conclude.
But because the participants were hospitalized throughout the study, so whether the procedure would prevent relapse for addicts in their usual environment remains to be tested, Costandi writes in his report for Nature.
In a commentary published along with the new study, two Cambridge University researchers write: “Remarkably, the authors successfully (applied) the approach to a population of heroin addicts. Only the group that had the 10-minute delay between the heroin video and (training) showed a marked reduction in craving and blood pressure after presentation of heroin-related cues at every time point tested.
But because cue-related craving isn’t the only thing that causes former drug dependents to relapse, this new technique isn’t a complete “cure.” It’s best done in a rehab or in another supportive situation, so that recalling cues doesn’t simply prompt immediate relapse, the Cambridge researchers say.
The new study builds on earlier research by Dr. Joe LeDoux and Dr. Liz Phelps of New York University, which showed that memories are reconsolidation during an early time window — and can also be “edited” at this point. In 2009, the Dr. LeDoux and colleagues published a study showing that interfering with reconsolidation can weaken fear memories in rats. The following year, he worked with Dr. Phelps on a follow-up study demonstrating the same process in humans.
“We used a very simple classical conditioning paradigm in which a blue square was paired with a mild electric shock to the wrist,” Dr. Phelps explains. This caused the participants to associate the square with the shocks — and to respond with fear when shown the square on its own.
The participants were then put through extinction sessions — they were shown the square without receiving shocks. One group was briefly shown the square 10 minutes earlier, to trigger reconsolidation of the fear memory right before the training. The others saw the square six hours before the training.
“We did the extinction training during reconsolidation, and what seems to have happened is that we somehow updated the old fear memory,” Phelps tells The Guardian. “In those particular subjects we didn’t see any evidence of the fear memory returning. We brought the subjects back a year later and showed that the fear did not come back in the group that got extinction during reconsolidation.”
“The new procedure is a variation on this, but also manipulates reconsolidation of addicts’ memories of past drug use to weaken their habitual responses to paraphernalia and other drug-related stimuli,” Costandi says.
“It’s a fantastic and fascinating study, involving very well controlled experiments in both rats and humans, and they got such dramatic results,” neuroscientist Phelps says.
“I wasn’t convinced that the technique would be effective in a clinical setting or in complex, real-life situations,” says Phelps. But she tells Nature she was “pleasantly surprised” by the positive results from the Chinese-American team.
The next steps? Lu says his team would like to see if the approach is applicable to other drugs — like alcohol and nicotine– and investigate the underlying neural mechanisms, as well.