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MUSC study finds protein linked to cocaine withdrawal

Peter Kalivas, Ph.D., and colleagues have identified a molecular mechanism that may contribute to the brain pathology associated with cocaine addiction.

Published in the April 22 issue of Neuron magazine, the study provides new insight into the processes that underlie withdrawal from repeated cocaine administration and may help explain events in the brain that contribute to the relapse of drug abuse.

“This is among the first manipulations in terms of relapse and withdrawal in the cognitive area of the brain,” Kalivas said. “The area, or prefrontal cortex  (PFC), is involved with making important decisions. By manipulating the protein AGS3, we were able to regulate drug-seeking behavior in an animal model of relapse. This has the potential for development in treating cocaine addicts and repressing the urges associated with relapse.”

There is no current drug therapy to successfully treat cocaine addiction; however, dysfunction in the PFC has been implicated in drug addiction, and research indicates that abnormal signaling through cellular proteins called G proteins may also be linked to cocaine addiction.

The researchers found that AGS3 is elevated in a rat’s PFC during withdrawal from repeated cocaine exposure. When AGS3 was artificially elevated in the PFC of normal rats, they manifested the same behavioral and cellular changes demonstrated in cocaine addicted animals. 

In addition, when cocaine-withdrawal-induced elevations of AGS3 were blocked, signaling was normal and cocaine-induced relapse and behavioral changes were prevented.

“It is clear that AGS3 levels in the PFC have a profound influence on cocaine addiction and relapse. The data in this study demonstrate that the level of AGS3 within the PFC can serve as a gatekeeper of the expression of behaviors associated with the addiction to cocaine,” Kalivas said. 

Friday, April 30, 2004
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