Using a chemical that blocks the creation of memories, scientists have prevented rats from using cocaine after they had become addicted to the drug. The hope is that doctors will one day be able to give humans some version of the chemical and stop cocaine addiction in its tracks.
Barry Everitt, an experimental psychologist at the University of Cambridge in England, focused his group's efforts on proteins called NMDA-type glutamate receptors in rat brains. Previous work on addiction and post-traumatic stress has shown that these proteins—which are found on the surface of brain cells—are essential to memory formation. The receptors are also crucial to reconsolidating a memory—moving it from its storage area in long-term memory to brain regions that handle short-term memory.
The researchers—who report their findings in the Journal of Neuroscience—put rats in a cage with a lever in it for a couple of hours per day for a week. When the animals pushed the lever, a light would come on and a cocaine solution would be dispensed to the rat. The rats began to associate the light they saw with cocaine.
After a couple weeks of forced sobriety, the animals were returned to the cage. Before going back in, some of the rats received injections of experimental drugs that block NMDA-type glutamate receptors in the amygdala—a brain region that has been implicated in drug-associated memories.
Both treated and untreated animals, when back in the cage, would press the lever over and over again. The light would come on, but no cocaine would be served. Untreated animals continued unfazed, hoping cocaine would eventually come out.
For the treated animals, however, Everitt says, "They press the lever, but it doesn't do anything, so they stop." The animals seemed to forget that the light in the cage meant cocaine was on its way for up to four weeks after only a single treatment.
Scientists say that suggests that by disrupting the recollection of a drug-associated memory—a person one abuses drugs with, a place that one uses drugs at, for example—a therapeutic may be able to break the connection between cues in the environment and the need for drugs. Sometimes these cues can be quite close to home—a family member or loved one.
Yavin Shaham, a neurobiologist at the National Institute on Drug Abuse in Bethesda, Md., said in a press statement that the new work is an example of "basic research that can be readily translated to the treatment of cocaine addiction in humans."
With no approved medications on the market to specifically treat cocaine addiction, most treatment regimens rely of behavioral therapy. Often, according to Everitt, these therapies involve exposing addicts to cues that they associate with drug use—but in the absence of the illicit substance. Once a recovered addict encounters these cues back in the real world though, they often relapse. Everitt suggests using an NMDA-type glutamate receptor blocker in the clinic could improve that treatment.
Karim Nader, a behavioral neuroscientist at McGill University in Montreal, called the new research "promising" for treating addiction, adding that he doesn't know of a one-time treatment that causes rodents to stop taking drugs for long periods of time.
Everitt notes that while the drugs used in the current study are experimental, there are several drugs approved by the U.S. Food and Drug Administration that target the same receptors: Dextramethorphan, which is found in many over-the-counter cough suppressants and memantine, a drug approved to slow the progression of Alzheimer's disease, are examples.
Erasing out memories linked to drug-taking may one day help recovering addicts to stay "clean".
Scientists were able to reduce drug-seeking behaviour in rats by blocking a memory molecule in the brain.
The research could lead to memory-control drugs that could be taken when addicts are most at risk of surrendering to their cravings.
Memories exist in different states depending on whether they are being recalled or not. During recall, they can be altered or erased through a process called "reconsolidation".
Scientists hope that employing this technique to block recollections of drug-related memories may help stop reforming addicts falling back into drug-taking. Such relapses are often triggered when addicts summon up drug-associated memories.
In a series of experiments, the Cambridge scientists trained rats to associate the switching on of a light with cocaine. The addicted rats were then exposed to the light, thereby "reactivating" the memory of cocaine even when the drug was not present. Subsequently in an effort to receive more cocaine, the rats would perform tasks which resulted in the light being turned on.
Next the animals were given a chemical that blocked receptor molecules in the brain with a key role in memory. Receptors are like "switches" which trigger biological events when particular chemicals bind onto them.
When rats received the chemical prior to the "reactivation" session their cocaine-seeking behaviour was curbed. A single treatment reduced or stopped their obsession with turning on the light for up to four weeks.
Blocking the receptors after or without the reactivation session had no effect on drug-seeking behaviour. This showed that drug-associated memories can only be disrupted at the time they are recalled.
The findings were published in the Journal of Neuroscience.
13-08-2008, 11:25
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