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Cocaine: Why Once Is Never Enough

WebMD Health News

May 30, 2001 -- After mice are given a single dose of cocaine, there are dramatic changes in brain regions crucial to drug addiction. These changes may help explain why even casual cocaine use can so easily mushroom into an all-consuming addiction, according to a research report in the May 31 issue of Nature.

"Just one dose of cocaine causes an enormous, very profound change in areas of the brain known to be important in addiction," study researcher Mark A. Ungless, PhD, a postdoctoral fellow in neurology at the University of California, San Francisco, tells WebMD. "People think that after the 'high' wears off, their brain is back to normal -- but it's just not true."

After one dose of cocaine, the strength of connections doubled between brain cells that signal each other using a chemical called dopamine. Surprisingly, these types of changes are very similar to those involved in normal memory, but occur in different brain regions. Even more astonishing, they lasted for at least a week.

"Drugs like cocaine tap into normal mechanisms of memory in a very effective, but harmful way," Ungless says. "We have to learn more about the differences to develop treatments for addiction and for memory disorders."

"This is an animal model, not human research, so we want to be conservative," researcher Antonello Bonci, MD, PhD, assistant professor of neurology at the University of California, San Francisco, tells WebMD. "But we're very excited about the implications for human addiction and relapse."

Other addictive behaviors like compulsive gambling and even marathon running may involve similar changes in related brain regions using dopamine, Ungless explains.

"Dopamine is involved in wanting things -- cravings increase when nerves using dopamine become more active," he says.

Why does cocaine use become addictive, often after a single dose? And why can addicts relapse into addiction after using again just once, even after long periods of staying sober? Ungless and Bonci still don't know for sure, but these brain changes involving dopamine give them some important clues.

"Every time you take the drug, you're in a vulnerable state, and the cravings and the brain response increase with each repeated exposure," Ungless says.

Mice given a second dose of cocaine on the following day were more hyperactive than they were after the first dose, and changes in connections between brain cells were more pronounced.

As the mouse is a good experimental model of human addiction, the increased brain response and behavioral change seen with each exposure to cocaine may help explain cravings that get stronger with repeated use. Additional research on specific changes in nerve cells may help develop potential new treatments.

So, it stands to reason that most humans become addicted after using cocaine just once?

"It ain't necessarily so," Edward J. Khantzian, MD, tells WebMD when asked for independent comment. "Cocaine, or any other addictive drug, is not universally appealing -- the response of each individual is highly variable. Each person has his drug of choice,"

Individual preference for specific drugs and the likelihood of becoming addicted after a single exposure are determined in part by genetics and in part by emotional makeup, says Khantzian, clinical professor of psychiatry at Harvard Medical School.

Depressed, withdrawn individuals may appreciate the energized, "high" boost they get with cocaine or other stimulant drugs. On the other hand, angry or anxious individuals may prefer the calming feeling of narcotics.

Nevertheless, discovering your drug of choice may be opening a Pandora's box best left closed, based on Ungless' research. Using drugs just once may trigger dramatic changes in the brain that catapult the user into addiction.

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