Chemical Blocks Memory-Related Drug Cravings

New Strategy for Developing Addiction Treatment

A novel chemical compound that blocks memory-related drug cravings has the potential to be the basis of new therapies to aid drug-addiction recovery efforts, UC Irvine neurobiologists have found.

Because exposure to people, places and objects previously associated with a drug habit can trigger overwhelming memory-based cravings, many former drug users often relapse into drug-taking behavior.

But a study led by John F. Marshall, a researcher in UCI's Center for the Neurobiology of Learning and Memory, shows that memory for places associated with cocaine use can be strikingly altered by inactivating a specific protein called ERK (extracellular signal-regulated kinase) in the brains of animals.

Especially significant is the finding that administering the inactivator compound immediately after recall of the cocaine-associated places also continued to blur memories of those places weeks later. This research provides novel insights into the brain mechanisms underlying relapse and suggests a new strategy for developing addiction treatments.

Drug-Addiction Therapies

"Our findings suggest that memories responsible for relapse in drug addicts may be similarly disrupted by a therapeutic agent targeting ERK or related proteins," Marshall said. "This work, however, is a first step toward subsequent efforts that can produce effective drug-addiction therapies." In the study, Marshall and graduate student Courtney A. Miller employed rats that shuttled between two distinctive environments, one which offered cocaine. Because of the drug's strong rewarding properties, these animals quickly learned which of the two compartments was associated with the cocaine and preferred to spend time in that environment.

Long-Lasting Effect

The researchers were then able to block the rats' strong memory for the cocaine-associated environment by infusing a drug that inactivates ERK – a chemical compound called U0126 – into a brain region that rewards learning. Most importantly, this inhibitory effect was long lasting, with the memory blocked for at least two weeks after the single infusion.

Continuing research by Marshall and his colleagues investigates how this ERK inactivation affects the brain to block memory for cocaine-associated places.

Study results appear in the Sept. 15 issue of Neuron.