The threat of relapse hangs over any attempt to kick a heroin addiction. The results of a new study provide new clues as to which drug users may be at greater risk of sabotaging their treatment efforts. Scientists have identified a gene that plays a crucial role in controlling heroin craving and relapse behavior in rodents.

The nucleus accumbens is a brain region important for processing pleasure and rewards; as such, it is central to heroin addiction. Using the drug activates the area, which is divided into a core and a shell, to produce effects that are both pleasurable and highly addictive. Ivan Diamond of the Ernest Gallo Clinic and Research Center in Emeryville, Calif., and his colleagues studied rats that ingested repeated doses of heroin and found that a gene known as AGS3 can increase the output of the signaling in some neurons that respond to the drug. When the researchers inhibited the expression of AGS3 in the nucleus accumbens core of animals that had previously experienced both addiction and withdrawal, they found that the rats showed less desire to seek out additional drugs after they were given a small dose. Interfering AGS3 expression in the shell of the nucleus accumbens did not dampen their desire for the drug, however.

The results build on work that previously implicated AGS3 in cocaine relapse as well. "These observations," the authors conclude, "open an avenue to develop treatments for heroin addiction directed against relapse." A report detailing the findings will be published online this week by the Proceedings of the National Academy of Sciences.

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