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Research Explores How Brain Suppresses Drug Cravings

Understanding Neural Ensembles in Infralimbic Cortex May Lead To Improved Addiction Treatment

For the nearly 20 million US adults addicted to drugs or alcohol, no effective medical treatment exists despite a growing body of scientific knowledge about the factors that trigger relapse.

It's a quandary that prompted a research quest for Nobuyoshi Suto, PhD, of Scripps Research's Department of Neuroscience.

Rather than continue to dig for clues on what drives relapse, Suto and his team flipped the problem: They explored how the brain responds to environmental cues that suppress—not promote—drug cravings, specifically for desires for alcohol and cocaine.

Their findings may contribute to better medicines to treat addiction, Suto says. The research, supported by grants from NIH's National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, was published in Nature Communications.

"Medications designed to counter brain processes that lead to relapse have seen limited success in patients, as have nondrug interventions such as cue-exposure therapy that seeks to help individuals deal with addiction triggers," Suto says. "We believed an alternate strategy would be beneficial, so we sought to explore what happens in the brain in the absence of triggers when cravings are not driving behavior."

The study examined how nerve cells behaved in the brain's infralimbic cortex, the region believed to be responsible for impulse control.

The scientists worked with male rats conditioned to be compulsive users of alcohol or cocaine. Suto and his team wanted to find out what happens in the brain when the rats received environmental cues—they used a citrus scent, in the case of this study—that drugs were not available. Those signals, known as "omission cues," were successful at suppressing all of the main factors that promote drug relapse.

The team then dug deeper into the underlying "anti-relapse" brain mechanisms, using a laboratory technique that would remove any ambiguity about what role the neurons play in shaping behavior. "Our results conclusively establish that certain neurons that respond to omission cues act together as an ensemble to suppress drug relapse," Suto says.

"Our hope is that further studies of such neural ensembles—as well as the brain chemicals, genes and proteins unique to these ensembles—may improve addiction medicine by identifying new druggable targets for relapse prevention."

Source: EurekAlert! Science News, Sept. 9

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