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New Gene Therapy Could Help Quell Alcoholic Cravings

One prevailing view of addiction holds that alcohol and other drugs alter the way dopamine works in the brain. These substances increase the brain's production of dopamine, a neurotransmitter associated with feelings of pleasure and reward. But at the same time, they deplete the number of available D-2 dopamine receptors, which are necessary to appreciate the buzz excess dopamine can bring. As a result, addicts try to increase their intake to compensate for a blunted pleasure response¿all the time.

A new study from Panayotis Thanos and colleagues at Brookhaven National Laboratory has found that restoring depleted D-2 receptors in the brains of 'alcoholic' lab rats, even temporarily, can quell the animals' cravings. "This is a preliminary study, but when you see a rat that chooses to drink 80 to 90 percent of its daily fluid as alcohol, and then three days later it's down to 20 percent, that's a dramatic drop in alcohol intake¿a very clear change in behavior," Thanos says. "This gives us great hope that we can refine this treatment for future clinical use."

The researchers introduced the gene for the D2 receptor directly into the pleasure centers of the rats' brains using a modified virus. Brain scans revealed that the animals developed higher levels of D2 receptors within three to four days, and then returned to normal eight days after the injection. Among rats trained to take alcohol instead of water, the gene therapy reduced their preference by 43 percent. These animals also drank 64 percent less alcohol than rats that received placebo injections. Even rats with low preference for booze drank significantly less after treatment.

The effects of the gene therapy wore off in a week, but fresh injections put the rats back on the wagon. "This is the first evidence that overproduction of D2 receptors reduces alcohol intake," Thanos says, "and suggests that high levels of D2 may be protective against alcohol abuse in humans."

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