New Study Reveals How Drugs Manipulate Brain’s Natural Reward Mechanisms
Summary
Researchers have made significant advances in understanding how drugs like cocaine and morphine disrupt the brain’s natural reward mechanisms. A recent study using advanced neuroscientific techniques in mouse models has tracked how neurons in the nucleus accumbens respond to both natural rewards and drugs. The findings not only deepen our understanding of addiction but also identify potential targets for innovative addiction treatments.
Key Facts
- The study identifies specific neurons in the nucleus accumbens that are affected by both natural rewards and drugs, explaining the mechanism behind the powerful grip of addiction.
- Advanced tools allowed researchers to observe how repeated drug exposure alters neuronal responses, increasing the preference for drugs over natural rewards.
- The findings point to the mTORC1 signaling pathway and the Rheb gene as potential therapeutic targets, offering hope for new addiction treatments.
Study Highlights
Mount Sinai researchers, in collaboration with scientists at The Rockefeller University, have uncovered a mechanism in the brain that allows cocaine and morphine to take over natural reward processing systems. The findings of this groundbreaking research, published in Science, shed new light on the neural underpinnings of drug addiction and could offer new mechanistic insights to inform basic research, clinical practice, and potential therapeutic solutions.
“While this field has been explored for decades, our study is the first to demonstrate that psychostimulants and opioids engage and alter the functioning of the same brain cells that are responsible for processing natural rewards,” explains senior author Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience, Director of The Friedman Brain Institute, and Dean for Academic Affairs of the Icahn School of Medicine at Mount Sinai, and Chief Scientific Officer of the Mount Sinai Health System.
“These findings provide an explanation for how these drugs can interfere with normal brain function and how that interference becomes magnified with increasing drug exposure, ultimately redirecting behavior compulsively towards drugs—a hallmark of addiction pathology,” Nestler adds.
The study focused on identifying convergent mechanisms of addiction in mouse models across two different classes of drugs: cocaine, a psychostimulant, and morphine, an opioid.
This groundbreaking work required the amalgamation of a highly interdisciplinary team, organized by Dr. Nestler and long-time collaborator Jeffrey M. Friedman, MD, PhD, Marilyn M. Simpson Professor at The Rockefeller University and an investigator of the Howard Hughes Medical Institute. The team employed a suite of cutting-edge tools and methodologies spanning behavioral, circuit, cellular, and molecular domains of neuroscience.
Through these innovative efforts, the researchers were able to track how individual neurons in a forebrain region called the nucleus accumbens respond to natural rewards like food and water, as well as to acute and repeated exposure to cocaine and morphine in a cell-type-specific manner.
They discovered a largely overlapping population of cells that respond to both addictive drugs and natural rewards and demonstrated that repeated exposure to the drugs progressively disrupts the cells’ ability to function normally. This disruption results in behavior being directed toward drug-seeking and away from natural rewards.
“By tracking these cells, we show that not only are similar cells activated across reward classes, but also that cocaine and morphine elicit initially stronger responses than food or water, and this actually magnifies with increasing exposure,” notes co-first author Caleb Browne, PhD.
The research team also identified the mTORC1 intracellular signaling pathway as a facilitator of the disruption of natural reward processing by drugs. Additionally, they discovered the Rheb gene as a potential mediator of this relationship, providing a novel therapeutic target for future research.
In conclusion, these findings have significant implications for addiction neuroscience, offering a clearer understanding of the effects of drugs on the brain and potential avenues for the development of more effective addiction treatments.
