Frontier: Reactivating memories may fight addiction

by Sandra A. Swanson

September, 2008

Disrupting retrieval of drug-related memories in animals may spur more effective addiction treatments.

A study published in the Aug. 13 Journal of Neuroscience expands on previous experiments showing that memories can weaken during the retrieval process, requiring “reconsolidation” to restabilize. “Retrieval is an active process: you’re using the same neurocircuitry to read the memory that you used to make it in the first place,” says Amy Milton of the University of Cambridge, the study’s lead author.

To test memory’s malleability, Milton and her colleagues used drugs (D-APV and MK-801) to block NMDA receptors, which help form memories, during retrieval in rats. The rats self administered cocaine and learned to associate the drug with the appearance of a light. To solidify that pairing of light and drug, each rat received 180 to 300 cocaine infusions.

Later, researchers “reactivated” those memories by triggering the light but replacing the cocaine with a saline solution, during a brief memory reactivation session. In memory alteration, the receptor blockers’ timing proved critical. A group of rats received the drugs prior to reactivation, and that single session prevented relapse for at least a month.

Another group received the blocker immediately after memory reactivation; that approach did not prevent relapse. Milton notes that this contradicts previous studies suggesting that memories are still mutable right after retrieval. One possible explanation: While other experiments used very brief (e.g. 90-second) reactivation sessions, these lasted 15 minutes—still brief relative to the rats’ previous history of cocaine taking.

The results highlight NMDA receptors’ time dependence. “By the end of the reactivation session, the memory has already probably started to restabilize, which is why we didn’t see an effect,” Milton says.

These findings could also have implications for treating psychiatric disorders and perhaps obesity, Milton says: “The neurobiological mechanisms are thought to be similar between some forms of obesity and drug addiction, so it could be a useful treatment for stopping people from overeating.”