Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mount Sinai researchers find promising new drug targets for cocaine addiction

21.01.2014
For first time, PARP-1 enzyme, Sidekick-1 gene implicated in enhancing brain reward system

Researchers 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 changes—changes made by enzymes—that 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.

Diane Damez-Werno, Haosheng Sun, Ningyi Shao, Amy Gancarz, Clarisse Panganiban, Caroline Dias, JaWook Koo, Paola Caiafa, Lewis Kaufman, Rachael Neve, David Dietz and Li Shen are additional study coauthors.

The US National Institute of Drug Abuse (P01DA008227) supported this research.

About the Mount Sinai Health System

The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care.

The System includes approximately 6,600 primary and specialty care physicians, 12-minority-owned free-standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.

Laura Newman | EurekAlert!
Further information:
http://www.mountsinai.org

More articles from Health and Medicine:

nachricht Discovery points to a new path toward a universal flu vaccine
03.07.2015 | Rockefeller University

nachricht "CCS Telehealth Ostsachsen", Germany's largest telemedicine project, goes online in Dresden
02.07.2015 | Universitätsklinikum Carl Gustav Carus Dresden

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Viaducts with wind turbines, the new renewable energy source

Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.

The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions

A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Siemens receives order for offshore wind power plant in Great Britain

03.07.2015 | Press release

'Déjà vu all over again:' Research shows 'mulch fungus' causes turfgrass disease

03.07.2015 | Agricultural and Forestry Science

Discovery points to a new path toward a universal flu vaccine

03.07.2015 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>