Drugs like morphine and cocaine fundamentally warp the brain’s reward system—creating the urge to use while, simultaneously, throwing natural urges to eat and drink off-kilter.

Now, scientists from The Rockefeller University and Mount Sinai have identified, for the first time, a common reward pathway that may serve as a hub for rearranging such fundamental priorities. The findings, published in Science, shed light on neural processing of diverse classes of rewards in mice, with potential implications for understanding substance use disorders in humans.

“We’ve known for decades that natural rewards, like food, and drugs can activate the same brain region,” says Rockefeller’s Jeffrey F. Friedman. “But what we’ve just learned is that they impact neural activity in strikingly different ways. One of the big takeways here is that addictive drugs have pathologic effects on these neural pathways, that’s distinct from, say, the physiologic response to eating a meal when you are hungry or drinking a glass of water when you are thirsty.”

Homing in on the reward circuit

Nestled in the forebrain, the nucleus accumbens (NAc) is involved in processing rewards from and desire for food, sex, social interaction—and addictive substances. The NAc, in close collaboration with the pleasure and mood modulating neurotransmitters dopamine and serotonin, influences decision-making by integrating motivation, reinforcement, and pleasure, essentially encouraging animals to repeatedly pursue activities that routinely feel good.

“The NAc is a key node where the underlying dopaminoceptive neurons direct and refine animals’ behaviors towards their goals,” says Bowen Tan, a graduate student in Friedman’s lab. “What we hadn’t been able to understand is how repeated exposure to drugs corrupts these neurons, resulting in escalated drug-seeking behaviors and a shift away from healthy goals.”

To answer that question, Friedman and Tan teamed up with Mount Sinai’s Eric J. Nestler, a psychiatrist and expert on the molecular neurobiology of drug addiction and depression. Together they turned to Rockefeller’s Alipasha Vaziri to overcome technical limitations that have hampered past work in the field. Brain imaging techniques developed in Vaziri’s lab are among the only tools capable of capturing the majority of the mouse cortex in real-time with high resolution. But in this case, the researchers also needed the capability to record neurons at large tissue depths, in order to image the neural activity at single-cell resolution in the NAc.

“Advancing our understanding of the intricately connected network within the brain demands the innovation of cutting-edge imaging technologies that can capture neuronal activity across distant brain regions, but also that of those at deeper regions,” Vaziri says.