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Scientists have found a way to interfere with the pleasure your brain feels from drinking alcohol. This ScienCentral news video has more.
Here's to Good Health
It isn't uncommon for us to pop open a bottle of Champagne on a happy occasion or break out a beer when watching our favorite team play an important game. Alcohol has been a part of our celebrations for over 10,000 years. Side by side however, alcohol abuse has also been around, with references to it in ancient Egyptian writings and the Old Testament. Up until the 18th century, drunkenness was believed to be a result of weak will power, not thought of as an illness. But today, with growing evidence of its ill effects, excessive drinking has been deemed a disease. Magnus Huss, a Swedish researcher, coined the term alcoholism in the mid 19th century.
When scientists began to think of ways to deal with such strong addictions they turned to a basic question — what makes people get hooked on alcohol? Researchers found that alcohol increases the amount of certain brain chemicals including dopamine, often associated with pleasure and addiction. These chemicals impact us by attaching to proteins called receptors, creating what is often referred to as a "reward circuit," sending out the pleasure signals.
Dopamine receptor image: Brookhaven National Laboratory
Dopamine has five receptors in the brain, of which the D2 receptor has an established role in alcoholism. Neuroscientist Panayotis Thanos of Brookhaven National Laboratory has now added another of its receptors, D3, to the band of culprits in this disease.
A new drug that blocks D3 without affecting any of the other receptors, allowed the researchers "for the very first time," says Thanos, "to look at specifically the dopamine D3 receptor and its role in alcohol abuse." He hypothesized that "treating with this drug would also lead to decrease of alcohol drinking."
To test the hypothesis, Thanos and his team monitored ten rats, genetically modified to prefer alcohol and ten non-preferring rats. They could choose between pure water and water mixed with 15 percent alcohol — slightly stronger than wine. "The alcohol preferring animals would be comparable to drinking many glasses of wine --- strong wine --- and of course a resulting increase in blood alcohol, resembling what a person would get after a long night of binging on alcohol," Thanos explains.
After two weeks Thanos treated them with three doses of the drug that blocks dopamine from binding to D3, and thus short circuits the reward pathway. He tracked alcohol intake by measuring blood alcohol levels at various times in the experiment. He also monitored the rats' behavior in terms of alcohol preference by hooking up a computer to the two bottles that could automatically count the number of times the rats' tongues touched the bottle.
Panayotis Thanos
Thanos found that the medium and high doses had an interesting effect, not only in the alcohol-preferring rats but also in the non-preferring rats. "We found that the alcohol preference and alcohol intake was diminished almost by half," he says.
Stephen Rayport, associate professor of psychiatry and neuroscience at Columbia University Medical Center, notes that while this is preliminary research, it points to a particular brain receptor to target and potentially help alcoholics. "This is very exciting kind of work because the whole hope of the different types of dopamine receptor classes or subtypes was that you would be able to target a specific function, get your therapeutic effects without side effects if you can be more selective," he says. Rayport feels this technique could have more value than present day treatments, which make alcoholics feel sick in order to stop them from drinking. By blocking the pleasure one feels from drinking, Rayport explains, "all it did was just to reduce the repetitive drive to seek the alcohol, as apposed to invoke these adverse consequences."
Thanos concedes that dopamine is one of many chemicals that make up the reward network in our brain, but emphasizes that the best way to get a handle on this network is to study the individual circuits and their contribution to the mechanism of alcoholism. "It is really only after we have a concrete understanding of these neurotransmitter systems individually and their respective receptors that we can then try and look at them as a whole, and be able to come up with a ranking or understand better which of these and their receptors are more involved or less involved. And I think that is an important step to take in order to come up with an affective treatment of alcohol and other drugs of abuse," explains Thanos.
Rayport points out however, that while the drug used in the experiment is selective for one particular receptor, it is not very potent, as large amounts need to be used to have an effect. "I'm still left uncomfortable by how much they needed to use," says Rayport, adding that an important step would be to develop a drug effective at low doses. Thanos says that work is already in progress to find a better D3 blocker that could have clinical uses.
Thanos feels that another important step is to carry out longer experiments that better mimic alcoholism, which is a chronic disease. "We plan to continue the research looking at the effects of what happens to the dopamine D3 receptor with chronic alcohol consumption, as well as what happens to dopamine D3 during withdrawal, abstinence of alcohol and how that is really interrelated in the overall mechanism of alcoholism," explains Thanos.
So while there is nothing wrong with raising our glasses in celebration, Thanos hopes his research will keep people from refilling those glasses, dangerously often.
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