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Cocaine Damages the Brain's Pleasure Cells

Reaction severest in those who are depressed

THURSDAY, Jan. 2, 2003 (HealthDayNews) -- Cocaine users seek pleasure, but the more they indulge in the drug, the less likely they are to feel the pleasure they're seeking.

That's the finding of a new study that shows cocaine damages brain cells that trigger the feelings of pleasure. The drug also exerts its most serious effects on those who are clinically depressed, the researchers found.

This is the first time research shows what happens "in those humans with the most clinically significant cocaine dependency problems," says Dr. Karley Little, chief of the Veterans Affairs Healthcare System in Ann Arbor, Mich., and lead author of the study in the January issue of the American Journal of Psychiatry.

"Ninety-five percent of studies of drug abuse are in animals," he adds. "We're showing the change in humans."

The researchers looked at postmortem brain samples of 35 known cocaine users and 35 non-cocaine users, used as controls. All were matched for age, sex, race, and cause of death.

All of those known to use cocaine "had cocaine in their system when they died," although cocaine itself was not the direct cause of death in most cases, Little says. Many died in car accidents or of cocaine-related heart disease, and "a fair number were murdered."

What the brain samples showed is that those who took cocaine had problems with the amount of dopamine their brains produced, and how it was released by the brain.

Dopamine is a chemical known to be released to signal pleasure. "It is essential and coordinates pleasure," Little says, "but it's not the pure sensation."

Cocaine initially sets in motion changes in brain cells that disrupt the flow of dopamine. It blocks transporters that bring dopamine back into cells. This causes dopamine to build up outside of cells and bind with other receptors, signaling pleasurable feelings repeatedly. This explains the "high" that cocaine users crave, Little explains.

However, the continuous use of cocaine led to lower dopamine levels in the study subjects. Less dopamine was being produced, and there was less of the protein known as VMAT2, which lives in the cells and helps prepare dopamine to be released again. Finally, there was less indication that VMAT was available for binding.

The cells involved in the functioning of dopamine either fall asleep or die in those who regularly use cocaine, Little says.

While animal studies have indicated some of these brain changes, the change in humans is to a much more significant degree, he notes. "It's an overwhelming change in neurons. The changes in the VMAT protein are a little unprecedented," he says.

Another interesting finding is that "we found these changes correlate with a symptom." Notably, cocaine users known to be depressed had the most significant changes in their dopamine levels, Little says.

Seven of the cocaine users they examined had been diagnosed with depression, and these seven were the ones who showed the most striking decrease in dopamine being released and increase in reuptake of the chemical.

"We don't know why the reaction is more severe in the depressed," Little adds, but he speculates that they may have a different response to cocaine and "that's why it makes it harder for these people to stop. Our study is telling us a lot more about the worse patients."

The researchers next plan to count dopamine neurons to see if there are actually less of them in the cocaine users, Little says. He doesn't think the neurons have died off. "It's more likely they're turned way down. We're not sure if they go back to normal once a person stops taking cocaine," he adds.

Thomas W. Clark, a research associate at Health and Addictions Research, Inc., believes this study "helps to show cocaine addiction is a real physical problem. There are changes in brain function and structure consequent to cocaine use."

Little says the relevant message of his finding is that cocaine causes harm.

"It's important to convey to people who might be tempted to take cocaine that there's a chance they might damage part of their brain," he says.

What To Do

For more on cocaine's effect on the brain, visit the National Institute on Drug Abuse or Emory University.

SOURCES: Karley Little, M.D., chief of the VHAS Affective Neuropharmacology Laboratory, Ann Arbor, Mich.; Thomas W. Clark, research associate, Health and Addictions Research, Inc.; Boston; January 2003, American Journal of Psychiatry
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