Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps research team finds stress hormone key to alcohol dependence

26.01.2010
The findings suggest development of drug treatment for substance abuse

A team of scientists from The Scripps Research Institute has found that a specific stress hormone, the corticotropin-releasing factor (CRF), is key to the development and maintenance of alcohol dependence in animal models. Chemically blocking the stress factor also blocked the signs and symptoms of addiction, suggesting a potentially promising area for future drug development.

The article, the culmination of more than six years of research, will appear in an upcoming print edition of the journal Biological Psychiatry.

"I'm excited about this study," said Associate Professor Marisa Roberto, who led the research. "It represents an important step in understanding how the brain changes when it moves from a normal to an alcohol-dependent state."

The new study not only confirms the central role of CRF in alcohol addiction using a variety of different methods, but also shows that in rats the hormone can be blocked on a long-term basis to alleviate the symptoms of alcohol dependence.

Previous research had implicated CRF in alcohol dependence, but had shown the effectiveness of blocking CRF only in acute single doses of an antagonist (a substance that interferes the physiological action of another). The current study used three different types of CRF antagonists, all of which showed an anti-alcohol effect via the CRF system. In addition, the chronic administration of the antagonist for 23 days blocked the increased drinking associated with alcohol dependence.

Out of Control

Alcoholism, a chronic disease characterized by compulsive use of alcohol and loss of control over alcohol intake, is devastating both to individuals and their families and to society in general. About a third of the approximately 40,000 traffic fatalities every year involve drunk drivers, and direct and indirect public health costs are estimated to be in the hundreds of billions of dollars yearly.

"Research to understand alcoholism is important for society," said Roberto, a 2010 recipient of the prestigious Presidential Early Career Award for Scientists and Engineers. "Our study explored what we call in the field 'the dark side' of alcohol addiction. That's the compulsion to drink, not because it is pleasurable—which has been the focus of much previous research—but because it relieves the anxiety generated by abstinence and the stressful effects of withdrawal."

CRF is a natural substance involved in the body's stress response. Originally found only in the area of the brain known as the hypothalamus, it has now been localized in other brain regions, including the pituitary, where it stimulates the secretion of corticotropin and other biologically active substances, and the amygdala, an area that has been implicated in the elevated anxiety, withdrawal, and excessive drinking associated with alcohol dependence.

To confirm the role of CRF in the central amygdala for alcohol dependence, the research team used a multidisciplinary approach that included electrophysiological methods not previously applied to this problem.

The results from these cellular studies showed that CRF increased the strength of inhibitory synapses (junctions between two nerve cells) in neurons in a manner similar to alcohol. This change occurred through the increased release of the neurotransmitter GABA, which plays an important role in regulating neuronal excitability.

Blocking the Stress Response

Next, the team explored if the effects of CRF could be blocked through the administration of CRF antagonists. To do this, the scientists tested three different CRF1 antagonists (called antalarmin, NIH-3, and R121919) against alcohol in brain slices and injected R121919 for 23-days into the brains of rats that were exposed to conditions that would normally produce a dependence on alcohol.

Remarkably, the behavior of the "alcohol-dependent" rats receiving one of the CRF antagonists (R121919) mimicked their non-addicted ("naïve") counterparts. Instead of seeking out large amounts of alcohol like untreated alcohol-dependent rats, both the treated rats and their non-addicted brethren self-administered alcohol in only moderate amounts.

"This critical observation suggests that increased activation of CRF systems mediates the excessive drinking associated with development of dependence," said Roberto. "In other words, blocking CRF with prolonged CRF1 antagonist administration may prevent excessive alcohol consumption under a variety of behavioral and physiological conditions."

Importantly, in the study the rats did not exhibit tolerance to the suppressive effects of R121919 on alcohol drinking. In fact, they may have become even more sensitive to its effects over time—a good sign for the efficacy of this type of compound as it might be used repeatedly in a clinical setting.

The scientists' cellular studies also supported the promising effects of CRF1 antagonists. All of the CRF antagonists decreased basal GABAergic responses and abolished alcohol effects. Alcohol-dependent rats exhibited heightened sensitivity to CRF and the CRF1 antagonists on GABA release in the central amygdala region of the brain. CRF1 antagonist administration into the central amygdala reversed dependence–related elevations in extracellular GABA and blocked alcohol-induced increases in extracellular GABA in both dependent and naive rats. The levels of CRF and CRF1 mRNA in the central amygdala of dependent rats were also elevated.

Roberto notes that another intriguing aspect of the work is that it provides a possible physiological link between stress-related behaviors, emotional disorders (i.e. stress disorders, anxiety, depression), and the development of alcohol dependence.

In addition to Roberto, the paper, "CRF-induced Amygdala GABA Release Plays a Key Role in Alcohol Dependence," was co-authored by Maureen T. Cruz, Nicholas W. Gilpin, Valentina Sabino, Paul Schweitzer, Michal Bajo, Pietro Cottone, Samuel G. Madamba, David G. Stouffer, Eric P. Zorrilla, George F. Koob, George R. Siggins, and Loren H. Parsons, all of Scripps Research. For more information, see Biological Psychiatry. http://www.ncbi.nlm.nih.gov/pubmed/20060104?log$=activity

This research was supported by the National Institutes of Health's National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse (NIDA), as well as the Pearson Center for Alcoholism and Addiction Research and the Harold L. Dorris Neurological Research Institute, both 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, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is located in Jupiter, Florida.

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Studies and Analyses:

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Disarray in the brain
18.12.2017 | Universität zu Lübeck

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>