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:12/1/2015)... ... December 01, 2015 , ... Visage accelerates mobile ... wholly owned subsidiary of Pro Medicus Ltd. (ASX: PME), has announced they are ... of North America (RSNA) 2015 annual meeting through December 3 in Chicago, Illinois, ...
(Date:12/1/2015)... (PRWEB) , ... December 01, 2015 , ... ... that it has been selected as a finalist in this year’s Fierce Innovation ... FierceMobileHealthcare. Next IT Healthcare was recognized as a finalist in the category of ...
(Date:12/1/2015)... MA (PRWEB) , ... December 01, 2015 , ... Lutronic, ... release of Clarity, the latest addition to the devices for sale in the United ... 755 nm Alexandrite and long-pulsed 1064 nm Nd:YAG lasers, into a single platform that ...
(Date:12/1/2015)... ... December 01, 2015 , ... PYA’s latest ... Integration ,” addresses a main “pain point” for merging or aligning healthcare provider ... a deal is signed. This quick-read guidance suggests that failing to recognize ...
(Date:12/1/2015)... ... December 01, 2015 , ... PartnerTech , ... membership and leadership since 2008. Gary Bruce, President of PartnerTech North America, currently ... spent a significant amount of time in Sweden since joining PartnerTech based in ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... MARIETTA, Ga. , Dec. 1, 2015 ... purchase Dallas, Texas -based Tenet Healthcare,s ... WellStar Board of Trustees approved the strategic move following ... expand upon its proven clinical care models and patient ... improved access to healthcare to new communities. ...
(Date:12/1/2015)...  Eyeon Therapeutics has received a Notice of ... on a charged hydrophilic polymer developed at Particles ... has been shown to be safe and effective ... Mitchnick , MD, CEO states, "This second set ... in conjunction with a therapeutic agent.  Nanoparticles coated ...
(Date:12/1/2015)... Pharma Tech Outlook recently conducted a comprehensive ... Management Solution Providers - 2015 .  After careful consideration ... CIOs, VCs, analysts, and the Pharma Tech Outlook editorial ... 10 clinical data management solution providers (check out the ... 36 respectively). --> ...
Breaking Medicine Technology: