In a study of cocaine-addicted rats, Rutgers Brain Health Institute researchers have discovered a correlation between the number of neurons that produce orexin—a chemical messenger important for sleep and appetite—and addiction.

The study was published today in Biological Psychiatry.

Restoring the number of orexin neurons to normal, or blocking orexin signaling in the brain, made the rats no longer addicted, suggesting the increased orexin neurons to be essential brain changes that cause the addicted state. The findings identify a promising avenue for treating addiction with orexin-based therapies.

First author Morgan James, a postdoctoral research fellow at the Rutgers Brain Health Institute, and colleagues also found that mimicking the typical binge-like pattern of drug use—with access to cocaine on and off throughout the day—produced a model that reflected addiction in humans better than the “gold standard” of continuous access. Rats given intermittent cocaine demonstrated behaviors observed in human users, including increased motivation for cocaine—even when they received a painful shock to acquire the drug, depression- and anxiety-like behaviors, and ‘relapse’ after several months of abstinence.

“Remarkably, these ‘addicted’ rats had a greater number of brain cells that produce the neuropeptide orexin,” said James. The increased number of neurons was persistent, lasting for at least 6 months after cocaine use, which might explain why addicts often relapse following long periods of abstinence, he reported.

“The addicted brain appears to become more dependent upon this increased number of orexin neurons,” noted Gary Aston-Jones, director of the Brain Health Institute and the study’s senior author. “Lower doses of an orexin blocker were effective at decreasing addiction behaviors in these rats than in those with shorter access to cocaine and that were less addicted.”

When people think of addiction, they tend to focus on a single chemical messenger, dopamine, and the reward center of the brain. But this greatly oversimplifies the addiction process—a complex pattern of brain circuits and multiple brain chemicals contribute to the anticipation, experience, and seeking of reward.

“Viewing addiction as mediated by a single neurotransmitter in a single brain region is not only inaccurate, but it prevents us from harnessing the complexity of brain signaling mechanisms in the process of developing treatments for addiction,” said John Krystal, editor of Biological Psychiatry.

—Newswise