For recovering addicts, the sight of drug paraphernalia and other reminders can trigger intense cravings and relapses. Now, two studies with rats demonstrate that it's possible to weaken drug-related memories by interfering with molecular signals in the brain's reward pathways. The work is a long way from the clinic, but researchers say it hints at an exciting new approach to helping addicts kick the habit.
Both studies, published in the 15 September issue of Neuron, add to growing support for a process called memory reconsolidation. This controversial idea holds that each time a memory is recalled it becomes briefly vulnerable--and can be weakened by compounds that target certain genes or molecules in the brain.
To find out whether drug-related memories can be weakened during recall, Jonathan Lee and colleagues at the University of Cambridge, U.K., first introduced a group of rats to the pleasures of cocaine. The animals quickly learned that a glowing light appeared each time they scored a hit. When the rats subsequently visited a different chamber, they busily pressed a lever that turned on the light, even if no cocaine was forthcoming.
Next the researchers tinkered with some of the rats' memories. They injected the amygdala--a brain region involved in emotion and reward--with antisense DNA to silence a gene, Zif268, which has been implicated in learning and memory. These animals showed no preference for the light-giving lever, suggesting that they no longer remembered the link between the light and cocaine. As in other reconsolidation studies, this memory weakening effect only happened when the rats recalled the memory--by seeing the light--just after the injection.
In the other study, neuroscientists John Marshall and Courtney Miller of the University of California, Irvine, found that blocking an enzyme called MEK in another brain region reduced the amount of time rats spent in a chamber where they'd previously received cocaine. Both research teams say their findings may be the first steps towards future therapies in which addicts take a drug that blocks memory reconsolidation just before viewing drug-related images or videos, perhaps tailored to their own previous behavior.
"I think this is really encouraging," says Karim Nader, a neuroscientist at McGill University in Montreal, Canada. But many hurdles remain. Nader points out that the current methods--injecting compounds directly into the brain--are hardly acceptable for use in humans. And behavioral neuroscientist Ann Kelley of the University of Wisconsin, Madison, cautions that memories formed by years of drug abuse in human addicts may be harder to shake than the cocaine memories of the rats in these experiments.
Related sites
Cocaine
information from the National Institute on Drug Abuse
Marshall's
site
Lee's
adviser Barry Everitt's site
Kelley's
site
Nader's
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