Navigation Links
Mount Sinai researchers find promising new drug targets for cocaine addiction

New York, NYResearchers from the Icahn School of Medicine at Mount Sinai have identified a new molecular mechanism by which cocaine alters the brain's reward circuits and causes addiction. Published online in the journal Proceedings of the National Academy of Sciences by Dr. Eric J. Nestler, MD, PhD, and colleagues, the preclinical research reveals how an abundant enzyme and synaptic gene affect a key reward circuit in the brain, changing the ways genes are expressed in the nucleus accumbens. The DNA itself does not change, but its "mark" activates or represses certain genes encoding synaptic proteins within the DNA. The marks indicate epigenetic changeschanges made by enzymesthat alter the activity of the nucleus accumbens.

In a mouse model, the research team found that chronic cocaine administration increased levels of an enzyme called PARP-1 or poly(ADP-ribosyl)ation polymerase-1. This increase in PARP-1 leads to an increase in its PAR marks at genes in the nucleus accumbens, contributing to long-term cocaine addiction. Although this is the first time PARP-1 has been linked to cocaine addiction, PARP-1 has been under investigation for cancer treatment.

"This discovery provides new leads for the development of anti-addiction medications," said the study's senior author, Eric Nestler, MD, PhD, Nash Family Professor of Neuroscience and Director of the Friedman Brain Institute, at the Icahn School of Medicine at Mount Sinai. Dr. Nestler said that the research team is using PARP to identify other proteins regulated by cocaine. PARP inhibitors may also prove valuable in changing cocaine's addictive power.

Kimberly Scobie, PhD, the lead investigator and postdoctoral fellow in Dr. Nestler's laboratory, underscored the value of implicating PARP-1 in mediating the brain's reward center. "It is striking that changing the level of PARP-1 alone is sufficient to influence the rewarding effects of cocaine," she said.

Next, the investigators used chromatin immunoprecipitation sequencing to identify which genes are altered through the epigenetic changes induced by PARP-1. One target gene whose expression changed after chronic cocaine use was sidekick-1, a cell adhesion molecule concentrated at synapses that directs synaptic connections. Sidekick-1 has not been studied to date in the brain, nor has it been studied in relation to cocaine exposure. Using viral mediated gene transfer to overexpress sidekick-1 in the nucleus accumbens, investigators saw that this overexpression alone not only increased the rewarding effects of cocaine, but it also induced changes in the morphology and synaptic connections of neurons in this brain reward region.

The research opens the door to a brand new direction for therapeutics to treat cocaine addiction. Effective drug therapies are urgently needed. National data from the US National Institute of Drug Abuse reveal that nearly 1.4 million Americans meet criteria for dependence or abuse of cocaine.


Contact: Laura Newman
The Mount Sinai Hospital / Mount Sinai School of Medicine

Related medicine news :

1. As Lipitor Lawsuits Mount, Bernstein Liebhard LLP Notes Publication of New Study with Possible Explanation for Link between Statins and Diabetes
2. Mount Sinai Queens Names New Orthopaedics Dept. Chief
3. Da Vinci Robot Lawsuits Mount, as Bernstein Liebhard LLP Comments on AARP Robotic Surgery Concerns
4. Bernstein Liebhard LLP Launches New Transvaginal Mesh Lawsuit Website as Claims Continue to Mount in U.S. Litigations
5. Pradaxa Lawsuits Mount, as Claims in Federal Multidistrict Litigation Exceed 2,000, Bernstein Liebhard LLP Reports
6. 2014 GoPro Mountain Games Evolves the Family Friendly Mud Run and Adds BADASS Dash Obstacle Course Race to Competition Line-Up
7. As Tylenol Lawsuits Mount, Bernstein Liebhard LLP Notes New Study Finding that Acetaminophen Combined With Alcohol May Increase Risk for Kidney Damage
8. Gary C. Butts, MD Appointed Chief Diversity and Inclusion Officer for the Mount Sinai Health System
9. Icahn School of Medicine at Mount Sinai named to new NIH Stroke Research Network
10. Researchers at Mount Sinai Say a New Strain of Bird Flu Packs a Punch Even After It Becomes Resistant to Drugs
11. QuickMedical Introduces the New Detecto 7550 Wall Mount Fold-Up Platform Wheelchair Scale
Post Your Comments:
(Date:6/27/2016)... ... June 27, 2016 , ... A revolution is underway. ... transport experience for the millions of people who require these medical transport services ... industry through the use of technology. Now, SmartEMS has put forth an industry-changing ...
(Date:6/26/2016)... Michigan (PRWEB) , ... June 26, 2016 , ... On ... as sponsor of the 2016 Cereal Festival and World’s Longest Breakfast Table in Battle ... honor of the city’s history as home to some of the world’s leading providers ...
(Date:6/26/2016)... ... , ... Brent Kasmer, a legally blind and certified personal trainer is helping to develop a ... fitness app plans to fix the two major problems leading the fitness industry today:, ... type program , They don’t eliminate all the reasons people quit their exercise ...
(Date:6/25/2016)... ... 25, 2016 , ... Austin residents seeking Mohs surgery services, can now turn ... to Dr. Russell Peckham for medical and surgical dermatology. , Dr. Dorsey brings specialization ... selective fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey was under the direction ...
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency ... named Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm facility. ... Director of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... startling report released today, National Safety Council research shows ... plan to eliminate prescription opioid overdoses. Prescription Nation ... the worst drug crisis in recorded U.S. history, assigned a "Making ... , New Mexico , Tennessee ... states, three – Michigan , Missouri ...
(Date:6/23/2016)... -- Bracket , a leading clinical trial technology and ... platform, Bracket eCOA (SM) 6.0, at the 52 nd ... 2016 in Philadelphia , Pennsylvania.  A demonstration ... of its kind to fully integrate with RTSM, will be ... is a flexible platform for electronic clinical outcomes assessments that ...
(Date:6/23/2016)... N.J. , June 23, 2016  Guerbet announced ... Premier Inc.,s Supplier Horizon Award . ... year, Guerbet was recognized for its support of Premier ... creation through clinical excellence, and commitment to lower costs. ... to receive this recognition of our outstanding customer service ...
Breaking Medicine Technology: