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In a groundbreaking collaboration between Mount Sinai researchers and scientists at The Rockefeller University, a pivotal discovery has been made regarding the neural underpinnings of drug addiction. Published online in Science on April 18, the study unveils a mechanism in the brain that enables drugs like cocaine and morphine to hijack natural reward processing systems, shedding new light on addiction pathology and potential therapeutic avenues.
Led by senior author Eric J. Nestler, MD, Ph.D., and co-senior author Jeffrey M. Friedman, MD, Ph.D., the study marks a significant milestone in understanding how addictive drugs interact with the brain’s neural circuitry. Dr. Nestler, the Nash Family Professor of Neuroscience and Director of The Friedman Brain Institute at Mount Sinai, elucidates, “Our study is the first to demonstrate that psychostimulants and opioids engage and alter functioning of the same brain cells that are responsible for processing natural rewards.”
By investigating mouse models exposed to cocaine and morphine, the research team identified overlapping populations of neurons in the nucleus accumbens—a forebrain region—responsible for responding to both addictive drugs and natural rewards like food and water. They observed that repeated drug exposure disrupts these neurons’ ability to function normally, skewing behavior towards drug-seeking and away from natural rewards.
Co-first author Caleb Browne, Ph.D., notes, “Cocaine and morphine elicit initially stronger responses than food or water, and this magnifies with increasing exposure, leading to disorganized responses to natural rewards after withdrawal from the drugs.”
Moreover, the study unveils a critical intracellular signaling pathway—mTORC1—implicated in the disruption of natural reward processing by drugs. Investigators identified the gene Rheb as a potential mediator of this relationship, offering a promising therapeutic target for future drug addiction treatments.
Dr. Friedman underscores the significance of the findings, stating, “Addictive drugs have pathologic effects on neural pathways distinct from physiologic responses to natural rewards like eating or drinking.”
The research team plans to delve deeper into addiction neuroscience, aiming to characterize molecular pathways critical for basic research and clinical practice. Their landmark dataset, integrating drug-induced neural activation with input circuit mapping, holds promise for the scientific community conducting substance use disorder research.
As Dr. Nestler concludes, “Understanding how drugs overtake the processing of natural rewards in the brain is crucial for developing effective treatments for addiction.”
The study, titled “Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need,” offers a significant stride forward in combating the global epidemic of drug addiction.
