Mount Sinai researchers have discovered how cocaine corrupts the brain and becomes addictive. These findings—the first to connect activation of specific neurons to alterations in cocaine reward—were published in Science on October 15. The results may help researchers in developing new ways of treating those addicted to the drug.
Led by Mary Kay Lobo, PhD, Postdoctoral Fellow in the Department of Neuroscience at Mount Sinai School of Medicine and first author of the study, researchers found that the two main neurons (D1 and D2) in the nucleus accumbens region of the brain, an important part of the brain's reward center, exert opposite effects on cocaine reward. Activation of D1 neurons increases cocaine reward whereas activation of D2 neurons decreases cocaine reward.
"The data suggest a model whereby chronic exposure to cocaine results in an imbalance in activity in the two nucleus accumbens neurons: increased activity in D1 neurons combined with decreased activity in D2 neurons," said Dr. Lobo. "This further suggests that BDNF-TrkB signaling in D2 neurons mediates this decreased activity in D2 neurons."
The study was conducted using optogenetics, a technology to optically control neuronal activity in freely moving rodents.
Opposite cocaine reward similar to those found when activating each neuron is achieved by disrupting brain-derived neurotrophic factor, which is a protein in the brain known for its involvement in neuronal survival, learning, and memory and drug abuse signaling through its receptor TrkB in D1 or D2 neurons.
"This new information provides fundamentally novel insight into how cocaine corrupts the brains reward center, and in particular how cocaine can differentially effect two neuronal subtypes that are heterogeneously intermixed in the nucleus accumbens," said Eric Nestler, MD, PhD, Chair of Neuroscience, Nash Family Professor, and Director of The Friedman Brain Institute at Mount Sinai and co-author on the study. "We can use this information to potentially develop new therapies for cocaine addiction, possibly aimed at altering neuronal activity selectively in either neuronal subtype."
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. U.S. News & World Report consistently ranks The Mount Sinai Hospital among the nation's best hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.
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