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December 21, 2004
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  Riddle of Addiction    

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National Institute on Drug Abuse

The Science Behind Drug Abuse

Exercise Addicts: When More is Less

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Americans seem to be fighting all kinds of different addictions these days, from alcohol and drugs, to food and exercise. Are we all addicted to something? Why does it happen? Does it have to be this way? Neuroscientists have been studying our brain responses to learn more about the mechanisms of addiction in the brain. Now, this ScienCentral News video reports how they are piecing together the "riddle of addiction".

Is there such a thing as a healthy addiction?

You may think you're addicted to chocolate, but if you can get through a day without it, it's merely love, and not addiction. Neuroscientists say that addiction is when you have no control over the craving and you feel you cannot function without it, even when you know it's bad for you. And underlying all addictions—whether they seem healthy, like exercise; or unhealthy, like narcotics—is a reward system in the brain.

"A lot of the brain chemicals that you see involved in drug addiction are also going on with natural forms of reward such as exercise and eating and sex," says Justin Rhodes, a postdoctoral fellow at Oregon Health & Science University's School of Medicine and at the Veterans Administration Medical Center in Portland. Rhodes wanted to see what natural forms of reward might indicate about the reward process of addiction, so he studied the effects of exercise on brain cells, or neurons, in mice.

Is exercise addiction healthy?
Scientists already know from studies in rodents that when mice have access to a running wheel, their brains make more of a chemical called brain-derived neurotrophic factor, and also produce more neurons in the hippocampus, the part of the brain that plays an important role in learning and memory. So Rhodes decided to crank up the exercise level. "We had been breeding mice for over 30 generations to display increased levels of voluntary wheel-running behavior," explains Rhodes. "We wanted to find out whether these mice that are running three times as much as normal would have even greater amounts of this chemical, and even more neurons in the brain, and even enhanced learning."

Rhodes and his team found that these super-exercising mice did have greater amounts of brain-derived neurotrophic factor and more neurons in the hippocampus. "The more they run the more brain chemical they have that supports and protects neurons, the more growth of new neurons they get," says Rhodes. However, this may not be enough to keep up with the stress of over-exercising.

"They are addicted to exercise," says Rhodes, who published this research in the journal Behavioral Neuroscience, "and it may be, in fact, that too much exercise can be damaging to the brain." Rhodes believes that the hippocampus is greatly activated by exercise, and the super-exercisers may run so much that there is too much stress to that area of the brain, maxing out its capacity to protect existing neurons or grow new ones. "There's only so many new neurons and only so much brain chemical that you can get with certain amount of running and they reach that max."

In fact, Rhodes gave the mice a learning test called the Morris water maze, in which both normal mice and super-exercising mice had to find a platform in a tank of colored water. To Rhodes' surprise, the exercise-addicted mice performed badly on the test, worse than the normal mice.

Dope and Dopamine

The release of excess dopamine can lead to addiction.
image: Brookhaven National Laboratory
If an exercise addiction can damage the brain, imagine what a drug addiction can do. A key brain chemical in addiction is dopamine, a brain chemical associated with the pleasure we get from eating, sex, and drugs. "That feeling gets reinforced, it seems to get stronger with time," says Jonathan Brodie, professor of psychiatry at New York University Medical Center and School of Medicine. "And then the pursuit of that feeling, the satisfying [nature] of that feeling causes people to take the drug again and again because they want to recapture that feeling. After a while it becomes more difficult to get that feeling and that's called tolerance. It takes more drug to get to the same place."

Now, some scientists are pursuing the idea that controlling dopamine might control the addiction. "The theory was that if you could help the brain to shut off dopamine a little more, then a drug like cocaine or methamphetamine wouldn't increase dopamine to the point where you'd get a euphoric response," says Stephen Dewey, senior scientist at the Brookhaven National Laboratory.

Brodie and Dewey think a drug developed for epilepsy in children, called GVG or gamma-vinyl-GABA that might do the trick. GVG is a chemical that increases another brain chemical called GABA which, in turn, shuts off dopamine. "What GVG does is that it makes it very difficult to get the release of the chemical responsible for, or associated with, a high," explains Brodie. "It inhibits, or blocks, the high response, the pleasure response."

After successfully testing GVG in monkeys, Dewey and Brodie, who published their research in the journal Synapse, treated a small group of cocaine addicts in Mexico with it (GVG has not been approved by the Food and Drug Administration for use in the U.S. even for epilepsy, although it is widely used in several other countries). "Somewhere around the third week, those people who stayed in the study reported the craving disappeared," says Brodie. "And the craving continues to be absent for the entire time of the study. Once they stopped craving, the craving didn't come back. And, even after the study was over, four weeks after they'd stopped taking any GVG, the craving had not returned. And they still were tested clean."

image: ABC News
"What we think the drug does is help you break a cycle," says Dewey. "[It] helps you with the craving, we think, and helps you with the reward." But he also points out, "you need to have psycho-social support throughout that process. You have to really desire to get off the drug."

Before any conclusions are drawn about the efficacy of GVG, more testing needs to be done. "We need to reproduce our findings," says Dewey, "and then it's essential that we go into a double-blind placebo-controlled trial, which is a large trial with many, many more people, many of whom are getting the actual drug and the other half who are getting the placebo. That will be our next step."

In the meantime, scientists will continue to search for clues in the brain to help solve the riddle of addiction whether the addiction is to something seemingly healthy or something clearly unhealthy.

Dewey and Brodie's study was funded by: The Biochemical Psychiatry Fund, New York University School of Medicine, the U.S. Department of Energy, and the National Institute of Drug Abuse. Rhodes's study was funded by: the National Science Foundation, National Institutes of Health Grants, the Christopher Reeve Paralysis Foundation, and the Lookout Fund.

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