A study by researchers at Rutgers Brain Health Institute identifies a promising avenue for treating addiction and provides clues to why people in recovery relapse

The discovery provides a promising avenue for treating addiction with orexin-based therapies.

Rutgers researchers have discovered a connection between cocaine addiction and the number of neurons that produce orexin, a neurotransmitter that regulates sleep and appetite.

In a study published in the journal Biological Psychiatry, researchers found that restoring the number of orexin neurons to normal, or blocking orexin signaling in the brain, made cocaine-addicted rats no longer addicted. The discovery provides a promising avenue for treating addiction with orexin-based therapies.

“These findings suggest that increased orexin neurons are essential brain changes that cause addiction,” says lead author Morgan James, a post-doctoral research fellow at the Rutgers Brain Health Institute.

According to the Centers for Disease Control and Prevention, in 2016 an estimated 5 million people aged 12 and older reported cocaine use in the past year and 10,375 people died.

Cocaine dependence is a difficult-to-treat, chronically relapsing disorder. The transition from casual drug use to addiction is often attributed to a gradual escalation of drug intake with repeated use. However, recent evidence indicates that the pattern of drug use, rather than simply the amount of drug intake, might drive addiction in humans.

The study was based on the behavior of experienced cocaine users, who report an intermittent pattern of intake, where even within a single binge, cocaine uses are separated by significant periods of time, resulting in a spiking pattern of cocaine levels in the brain.

The researchers mimicked this typical binge-like pattern of drug use—with access to cocaine on-and-off throughout the day—to produce a model that reflected addiction in humans. Rats given intermittent cocaine demonstrated behaviors observed in human users. This included 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.

The addicted rats had a greater number of brain cells that produce orexins. The increased number of these neurons was persistent, lasting for at least six months after cocaine use, which might explain why addicts often relapse following long periods of abstinence, James said.

“The addicted brain appears to become more dependent upon this increased number of orexin neurons,” said 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. The results of this study strongly implicate the orexin system in the addicted state and highlight this system as a promising target for addiction therapies.”

An increase in the number of orexin neurons was also seen in human heroin addicts in another recent study, indicating that this change in brain chemistry could be important in opioid addiction as well.