Researchers, in collaboration with scientists at The Rockefeller University, have discovered a mechanism in the brain that allows cocaine and morphine to hijack natural reward processing systems. The findings, published online in Science on April 18, shed new light on the neural underpinnings of drug addiction and could provide new insights for basic research, clinical practice, and potential therapeutic solutions.
“Our research has uncovered a groundbreaking discovery in the field, showing for the first time that psychostimulants and opioids impact the activity of the same brain cells involved in processing natural rewards,” said 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. “This insight sheds light on how these drugs disrupt normal brain function and how this disruption becomes intensified.”
the study’s main focus was on identifying shared mechanisms of addiction in mice models using two different types of drugs: cocaine, a psychostimulant, and morphine, an opioid. This innovative research involved bringing together a diverse team of experts, led by Dr. Nestler and Dr. Jeffrey M. Friedman, who is a Marilyn M. Simpson Professor at The Rockefeller University and an Investigator of the Howard Hughes Medical Institute. Dr. Friedman is also a co-senior author of the study. The team included a variety of members, such as two biophysicists: Alipasha Vaziri, PhD, Professor of Neuroscience and Behavior at The Rockefeller University and a co-senior author of the study, and Tobias Nöbauer, PhD, Assistant Research Professor at The Rockefeller University and a co-first author of the study. Working closely together, the team used advanced tools and methods across behavioral, circuit, cellular, and molecular aspects of neuroscience.
With these new approaches, scientists were able to monitor the behavior of individual neurons in a brain region known as the nucleus accumbens in response to natural rewards such as food and water, as well as to acThe researchers found that repeated exposure to cocaine and morphine affects specific cells in the body. These cells respond to both addictive drugs and natural rewards, and over time, the drugs disrupt the cells’ normal function, leading to behavior focused on seeking drugs rather than natural rewards. The study also showed that cocaine and morphine elicited stronger responses from these cells compared to food or water, and this response increased with more exposure.”notes co-first author Caleb Browne, PhD, a former Instructor in Dr. Nestler’s lab who is now a Scientist in the Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health (CAMH) in Toronto. “After withdrawal from the drugs, these same cells exhibit disorganized responses to natural rewards in a manner that may resemble some of the negative affective states seen in withdrawal in substance use disorder.”
Additionally, the research team identified an established intracellular signaling pathway — mTORC1 — that helps disrupt natural reward processing by the drugs. As part of that di
During their investigation, researchers identified a gene called Rheb which produces an activator for the mTORC1 pathway. This gene may play a role in the relationship between addiction and neuroscience, potentially opening up new possibilities for medical treatments in a field that currently lacks effective options.
The research team intends to further explore the cellular biology of addiction neuroscience in order to gain a better understanding of the molecular pathways that are crucial for both basic research and future clinical applications.
“Our work has also led to the creation of a significant dataset that combines drug-induced neural activation across the entire brain with input ci.The nucleus accumbens circuit mapping findings could be valuable for substance use disorder research, according to Bowen Tan, one of the co-first authors of the study and a graduate student in Dr. Friedman’s lab. “For years, it has been known that natural rewards such as food and addictive drugs can activate the same brain region,” says Dr. Friedman. “However, our recent discoveries show that they affect neural activity in significantly different ways. A key point here is that addictive drugs have abnormal effects on these neural pathways, which are different from the normal physiological response.”Eating when you feel hungry or drinking water when you’re thirsty,” says Dr. Nestler. He explains that their research will focus on how the brain processes information and how drugs can disrupt this process, leading to addiction.
