UCI Neurobiologists Find Treatment To Block Memory-related Drug Cravings

Becauseexposure to people, places and objects previously associated with adrug habit can trigger overwhelming memory-based cravings, many formerdrug users often relapse into drug-taking behavior.

But a studyled by John F. Marshall, a researcher in UCI’s Center for theNeurobiology of Learning and Memory, shows that memory for placesassociated with cocaine use can be strikingly altered by inactivating aspecific protein called ERK (extracellular signal-regulated kinase) inthe brains of animals. Especially significant is the finding thatadministering the inactivator compound immediately after recall of thecocaine-associated places also continued to blur memories of thoseplaces weeks later. This research provides novel insights into thebrain mechanisms underlying relapse and suggests a new strategy fordeveloping addiction treatments.

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

“Ourfindings suggest that memories responsible for relapse in drug addictsmay be similarly disrupted by a therapeutic agent targeting ERK orrelated proteins,” Marshall said. “This work, however, is a first steptoward subsequent efforts that can produce effective drug-addictiontherapies.”

In the study, Marshall and graduate student CourtneyA. Miller employed rats that shuttled between two distinctiveenvironments, one which offered cocaine. Because of the drug’s strongrewarding properties, these animals quickly learned which of the twocompartments was associated with the cocaine and preferred to spendtime in that environment.

The researchers were then able toblock the rats’ strong memory for the cocaine-associated environment byinfusing a drug that inactivates ERK – a chemical compound called U0126– into a brain region that rewards learning. Most importantly, thisinhibitory effect was long lasting, with the memory blocked for atleast two weeks after the single infusion.

Continuing research byMarshall and his colleagues investigates how this ERK inactivationaffects the brain to block memory for cocaine-associated places.

Marshallis professor of neurobiology and behavior in the UCI School ofBiological Sciences. The National Institute of Drug Abuse providedsupport for the study.