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$7M NIH grant for MUSC alcohol research center funds innovative treatments
Dawn Brazell | MUSC News Center | February 11, 2016


MUSC ARC - TMS
Photos by Sarah Pack

 
Dr. Colleen Hanlon, left,  demonstrates how researchers are using TMS  or transcranial magnetic stimulation to treat specific neural circuits in the brain believed to be involved in alcohol addiction.  

When it comes to alcohol, not all brains are created equal.

Someone all too familiar with that is MUSC researcher Colleen Hanlon, who is taking what’s known about neural circuitry to figure out why some people lose control of their drinking.

“The brain is an electrical organ. We have all these circuits firing all the time,” says Hanlon, Ph.D., who specializes in finding treatments for alcohol use disorders. The disorders are prevalent, devastating and difficult to treat, with high relapse rates that are likely caused by factors affecting the neural circuits governing craving and cognitive control, she says.

When a person with the disorder looks at an image of alcohol, brain imaging shows more areas light up than in the brain of someone without that disorder, says Hanlon, who is part of the departments of Neurosciences and Psychiatry and Behavioral Sciences at the Medical University of South Carolina.

Dr. Becker 
Dr. Howard Becker, director of MUSC's Alcohol Research Center, says national centers such as this push the frontier in finding better treatments to combat alcohol use disorders. 

Her research target: to see if activity can be increased in cognitive control areas or decreased in craving areas of the brain to help people escape a life affected by addiction, using transcranial magnetic stimulation.

“I’m super excited about it,” she says, “We’re pursuing a new line of therapy for psychiatry called magnetic medicine.”

Her research is just one of many projects being funded by the Charleston Alcohol Research Center’s new five-year, $7 million grant from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) at the National Institutes of Health. The research center, housed in the Addiction Sciences Division of the Department of Psychiatry and Behavioral Sciences, has sustained NIH support since it was first funded as a national Center of Excellence in 1995.

Research such as Hanlon’s shows why it’s critically important to have these centers, says Howard Becker, Ph.D., the center’s director. It is one of only 20 centers nationally and is the only one in the state.

“The center is tackling this really complex problem on a variety of fronts using all the sophisticated tools and technology that we have at our disposal to better understand how alcohol changes the brain and how, through understanding those adaptations, we can then better develop treatments that will be more effective in either reversing or rescuing some of that function that has gone awry due to chronic alcohol use.”

More than half of all adults have a family history of alcoholism or problem drinking, says Becker, who is a professor in the departments of Neurosciences and Psychiatry and Behavioral Sciences. However, despite the prevalence of this problem, the risk factors and ways in which alcohol alters brain function are not fully understood. Worse, there are very few treatments available for managing this disorder, he says.

 Charleston Alcohol Research Center
 Drs. Reggie Cannady and Jennifer Rinker conduct experimental work to examine how alcohol alters brain cell (neuronal) activity.

“Nationwide, alcohol use disorders constitute an enormous economic, medical and health care burden in our society. What is most important to emphasize is that alcohol is a brain disease, not a personal weakness. A unique feature of the Charleston ARC is that we blend basic research and clinical investigation to study this significant health problem.”

Understanding how changes in the brain underlie the transition from moderate controlled drinking to uncontrolled, compulsive drinking is critical for developing new and more effective treatment strategies for this disease, he says.

Heavy alcohol use alters activity in different regions of the frontal cortex and weakens executive, or decision-making, function. “When individuals engage in heavy risky drinking over time, the brain becomes highly reactive to sights and smells of alcohol, which drives the pleasurable response, but at the same time compromises the ability of the drinker to make responsible decisions about their alcohol drinking,” Becker says. “We’re interested in researching medications that could reverse that.”

Other research is focusing on the influence of genes in the development of alcohol use disorders and what clues they offer about which people will respond to certain medications. One research team led by Raymond Anton, M.D., is using brain imaging to examine whether people with a specific genetic makeup are more or less likely to respond to a medication that enhances behavioral control over drinking.

Meanwhile, ARC research teams led by John Woodward, Ph.D., and Judson Chandler, Ph.D., are probing different circuits in the frontal cortex that are altered by alcohol exposure and relate to impaired behavioral control over drinking.  These preclinical projects use a novel experimental approach involving DREADDs, or designer receptors exclusively activated by designer drugs.

MUSC ARC 
Behind Dr. Joe Schacht are images showing how alcoholics exhibit greater brain activation in response to alcohol cues compared to controls. This advanced neuroimaging technology is being used to evaluate the effectiveness of medications to reduce this brain activation. 

“We’re infecting cells with viruses to create receptors that respond to a drug, which have receptors that are otherwise inert. By doing that you can turn on or turn off activity in certain regions of the brain in a very selective way. We’re using that to see what happens to cortical circuits when we turn on or turn off certain regions in the brain as it relates to the way that it influences drinking.”

Becker describes it as the technology of the future in approaching brain disease. The drug is administered systemically, but will only be bioactive at those viral receptors. “We’re fooling the brain. It’s an extremely powerful approach,” he says, explaining that it will help figure out which sections of the brain are responsible for someone transitioning from being able to use alcohol for pleasure to becoming addicted.

All of this research points to a larger issue of how this is a brain disease, he says. “A lot of people don’t understand that.”

It’s too expensive a problem not to address, taking an estimated $250 billion toll on society not to mention the personal costs. Another problem is that fewer than 10 percent of people with alcohol use disorders seek treatment because of stigma and cultural pressures. “When someone comes in with hypertension, we don’t shun them because of their salt intake; when we treat diabetics, we don’t point our finger at them for sugar intake. That’s how we have to approach alcoholism, and treat it the same in terms of lifestyle changes and good medications.”

Part of that means training future researchers and clinicians to help change the culture. The center trains about 40 graduate and postdoctoral students in alcohol research over a typical five-year period. It is housed within the addiction science division, which has a robust clinical outpatient program. “It’s a walk-in unit, and you will be seen,” Becker says.

MUSC ARC 
This Acute Slice Electrophysiolgy Rig is used by ARC researchers to examine how alcohol alters brain cell activity. 
 
 

Another important center mission involves community outreach, especially providing information to thousands of primary and secondary school children about the science behind developing alcohol and drug addiction and the health consequences of drinking and using drugs during the adolescent years.

The hope is to prevent early drinking with its inherent risk of increased abuse and addiction, he says.

“It’s a uphill battle educating the public about the dangers of heavy drinking. Close to 90,000 deaths per year are alcohol-related, making it the fourth largest preventable cause of death in the U.S. Up to one-third of all emergency room visits are alcohol-related.”

That toll is too high, he says. That’s why the center puts researchers from basic science to translational and clinical research all together in an environment to feed off each other’s ideas.  

We put MUSC on the map on the national and international level because our scholars are internationally recognized. It’s nice to get that kind of recognition for the state and for MUSC," Becker says. "At the end of the day, the center is all about pushing scientific frontiers in understanding how alcohol changes the brain, with the ultimate goal being to develop new and better treatments to alleviate suffering in those afflicted with alcohol use disorders."


Did you know?

It takes centers, such as the one at MUSC, to make a dent in the impact of alcoholism in the community. Some of the center’s highlights:

  • Involved with clinical trials and FDA approvals of all medications (naltrexone, acamprosate, topiramate) used to treat alcoholism. Treated over 1,000 S.C. citizens with alcohol use disorders during these clinical trials over the last 20 years.
  • Discovered new medications (e.g. aripiprazole, gabapentin) to treat alcoholism and has worked with pharmaceutical companies (e.g. Lilly, Merck, Pfizer, Bristol-Myers Squibb) to discover new targets and compounds. MUSC’s Alcohol Research Center is the only NIH Center focusing on developing new medications to treat alcohol use disorders.
  • Developed a mouse model of alcohol dependence and withdrawal approved by the NIH-NIAAA to test medications for potential clinical use.
  • Proved in both mice and humans that repeated alcohol withdrawals lead to more serious withdrawals, seizures and earlier relapse. Showed that treatment of alcohol withdrawal with anticonvulsant drugs improves outcome and reduces addiction to typical anti-withdrawal medications (e.g. Valium, Librium).
  • Found that medications (e.g. naltrexone) that might be useful to reduce drinking might work best in people with a particular genetic profile, putting it at the forefront of pharmacogenomics or personalized medicine.
  • Became the first in the U.S. to measure and use a blood test, carbohydrate deficient transferrin, to detect and monitor heavy drinking. This blood test is now routinely used in addiction, general hospital and forensic settings.
  • Developed procedures to examine medication effects on enhanced brain reactivity to alcohol-related cues in alcoholics compared to social drinkers.
  • Showed that a history of personal trauma can serve as a risk factor for later alcohol abuse.
  • Demonstrated that heavy alcohol exposure alters specific circuits in the cortex that underlie impaired cognitive control and motivation for alcohol drinking.

 

 

 

 

 

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Dr. Raymond Anton talks about treatment options


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Resources >>

Charleston Alcohol Research Center

MUSC Center for Drug and Alcohol Programs

MUSC Department of Psychiary and Behavioral Sciences

NIAAA-funded research centers

MUSC News Center archives

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