Scientists may have figured out how addictive drugs like cocaine hijack the brain’s reward system to make us ignore basic needs like food or water. In mice, the researchers were able to extensively detail a neural pathway that allows the brain to respond to natural positive stimuli, while also showing how drugs can interfere with this pathway for the worse. The findings not only illuminate a key aspect of the addiction process but might help scientists someday find a safe and sustained way to short circuit it.
The research comes from scientists at The Rockefeller University and the Icahn School of Medicine at Mount Sinai. The team was hoping to better understand a critical stage of unhealthy drug dependence, when a person’s desire and need for a drug starts to take precedence over everything else.
“It is a long-standing observation that humans with substance use disorders fall into an ‘addiction cycle’ which progressively disrupts their healthy life,” lead author Bowen Tan, a researcher at Rockfeller’s Howard Hughes Medical Institute, told Gizmodo. “We began by asking a basic question: how do drugs of abuse interfere with basic needs?”
It’s already known that a region of the brain called the nucleus accumbens (NAc) helps regulate how we process and respond to rewarding and essential sensations like food. And past studies have found that potentially addictive drugs interact with the nucleus accumbens. For years, Tan and his colleagues have been working to unravel the exact network of brain cells in the NAc involved in this process. A 2022 study of theirs, for instance, found evidence in mice that the same set of NAc neurons help govern our sense of hunger and thirst.
In their latest study of mice, published Thursday in the journal Science, the authors found that two drugs of abuse—cocaine and morphine—activate these same cells. More than that, the repeated use of these drugs appears to progressively change the behavior of the cells over time, eventually warping the natural reward system and reducing the motivation for food and water in their mice subjects.
“We were able to combine a bunch of different advances in recent technologies that allow us to get a fine-grained resolution of how different brain cells are actually computing the value of naturally rewarding stimuli like food and water. And we could see how those same cells are altered by the drugs,” co-author Caleb Browne, a researcher at the Center for Addiction and Mental Health at Mount Sinai, told Gizmodo.
The team also managed to identify a specific gene tied to this neural pathway in the NAc, called Rheb, that likely plays a big part in allowing drugs to hijack the reward system. When the researchers disturbed Rheb (using the gene-editing tech CRISPR) in the lab mice, the drugs were no longer able to crowd out their need for food and water.
The findings are based on mice, so it will take more work to know for sure that a similar thing happens in humans who become addicted to these drugs. And while the hijacking of our reward system does contribute to substance use disorder, it’s not the only factor. But the team is hopeful that, by untangling the neurobiology of this process, we’ll be able to find better treatments for people struggling with addiction. The possibility that targeting Rheb alone could keep drugs from overriding our reward system is especially tantalizing, the researchers note, since it could mean that future treatments can avoid dampening our natural sense of desire.
“If you interfere at some level with addiction—it’s the same systems that make us motivated to do things. So if you shut down the motivation for drugs, that’s a challenge right now. I mean, you can do that, but then people won’t eat,” Browne said. “So this suggests that it might be important to look at this on a more granular level—that this might be an ideal way to target [addiction] without effects on natural behavior.”
The team plans to keep investigating the brain circuitry and chemistry underlying drug addiction. Future studies will try to figure out how other regions of the brain, especially those connected to higher order functions like memory and emotions, provide information to the reward-processing cells in the NAc, for instance. They also hope to study the potential role of these cells in making people vulnerable to relapse, even years after someone has stopped using the drug.
