Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps Research scientists find key mechanism in transition to alcohol dependence

01.06.2011
Finding could lead to development of drugs that decrease heavy alcohol consumption

A team of Scripps Research Institute scientists has found a key biological mechanism underpinning the transition to alcohol dependence. This finding opens the door to the development of drugs to manage excessive alcohol consumption.

"Our focus in this study, like much of our lab's research, was to examine the role of the brain's stress system in compulsive alcohol drinking driven by the aversive aspects of alcohol withdrawal," said Scripps Research Associate Professor Marisa Roberto, Ph.D., senior author of the study.

"A major goal for this study," added Research Associate Nicholas Gilpin, Ph.D., the paper's first author, "was to determine the neural circuitry that mediates the transition to alcohol dependence."

In the new research, published in the June 1, 2011 issue of the journal Biological Psychiatry, the Scripps Research scientists demonstrated the key role of a receptor —a structure that binds substances, triggering certain biological effects—for neuropeptide Y in a part of the brain known as the central amygdala. The amygdala, a group of nuclei deep within the medial temporal lobes, performs an important role in the processing and memory of emotional reactions.

"We've known for quite some time that neuropeptide Y is an endogenous [naturally occurring] anti-stress agent," says Markus Heilig, clinical director of the National Institute of Alcohol Abuse and Alcoholism (NIAAA). "We've also known that development of alcohol dependence gives rise to increased sensitivity to stress. This paper elegantly and logically brings these two lines of research together. It supports the idea that strengthening neuropeptide Y transmission in the amygdala would be an attractive treatment for alcoholism. The challenge remains to develop clinically useful medications based on this principle."

Discovering the Circuitry

Building on Gilpin's previous work on neuropeptide Y, in the new project, Gilpin, Roberto, and colleagues observed the effects of the administration neuropeptide Y in the central amygdala on alcohol drinking in rats. Alcohol-dependent rats were allowed to press levers for ethanol and water during daily withdrawal from chronic alcohol exposure.

"Normally, the transition to alcohol dependence is accompanied by gradually escalating levels of alcohol consumption during daily withdrawals," Gilpin explained. "The aim of this protocol was to examine whether neuropeptide Y infusions during daily withdrawals would block this escalation of alcohol drinking."

The scientists report a suppression of alcohol consumption with chronic neuropeptide Y infusions and detailed some of the neurocircuitry involved. Ethanol normally produces robust increases in inhibitory GABAergic transmission—GABA is another neurotransmitter—in the central amygdala, but this effect is blocked and reversed by neuropeptide Y.

Gilpin notes the scientists were surprised at one aspect of the findings—the role of a subset of neuropeptide Y receptors known as Y2 receptors. "Previous behavioral evidence suggested that antagonism of Y2 receptors in whole brain suppresses alcohol drinking, similar to the effects of neuropeptide Y," he said. "However, our data suggest that Y2 receptor blockade in central amygdala might actually increase alcohol drinking, presumably by affecting pre-synaptic release of GABA. These data also suggest that antagonism of post-synaptic Y1 receptors in central amygdala provides a viable pharmacotherapeutic strategy, a hypothesis supported by previous work from other labs."

Two additional aspects of the findings are worth noting, Roberto says. First, repeated neuropeptide Y administration not only blocked the development of excessive alcohol consumption in dependent rats, but also tempered the moderate increase in alcohol consumption following periods of abstinence in non-dependent rats. Second, neuropeptide Y exhibited long-term efficacy in suppressing alcohol self-administration, highlighting the potential of neuropeptide Y treatments for a clinical setting.

In addition to Roberto and Gilpin, authors of this paper, titled "Neuropeptide Y Opposes Alcohol Effects on GABA Release in Amygdala and Blocks the Transition to Alcohol Dependence" and scheduled to appear in the June 1, 2011 print edition of Biological Psychiatry, include Kaushik Misra, Melissa Herman, Maureen Cruz, and George Koob, all of Scripps Research. See http://www.ncbi.nlm.nih.gov/pubmed/21459365 .

This project was supported by the National Institutes of Health's National Institute on Alcohol Abuse and Alcoholism, and the Pearson Center for Alcoholism and Addiction Research at Scripps Research.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neuroscience, and vaccine development, as well as for its insights into autoimmune, cardiovascular, and infectious disease. Headquartered in La Jolla, California, the institute also includes a campus in Jupiter, Florida, where scientists focus on drug discovery and technology development in addition to basic biomedical science. Scripps Research currently employs about 3,000 scientists, staff, postdoctoral fellows, and graduate students on its two campuses. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, is ranked among the top ten such programs in the nation. For more information, see www.scripps.edu.

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

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: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>