Researchers have for the first time watched what happens in the human brain as an addictive drug--cocaine--creates first its "high" and then intense cravings for more of the drug. The images, published in tomorrow's issue of Neuron, reveal that cocaine affects much more complicated networks of brain areas than had previously been thought.
Addictive drugs hijack the brain's natural reward system, and studies with laboratory animals have pinpointed just a handful of regions where activity is most susceptible to drug-induced changes. But animal studies cannot separate the high, the craving, or any other "emotional" response. To see how human brain activity changes during these stages, Hans Breiter, Bruce Rosen, and Steven Hyman of Harvard Medical School and Massachusetts General Hospital in Boston and colleagues used functional magnetic resonance imaging, which measures blood flow in the brain and can reveal neural activity in fine detail.
The team scanned the brains of 10 cocaine addicts infused with either a salt solution or cocaine, while the subjects rated their feelings of euphoric "rush" and craving. When given the salt solution, the subjects experienced neither highs nor cravings, and just a few brain regions were activated. But cocaine induced both a rush, which peaked 3 minutes after infusion and rapidly dissipated, and also short-lived activity in a network of 92 brain areas. That was a surprisingly large number compared to what had been found in the animal studies, Breiter says. Then, over the next 10 minutes, as the subjects' cravings grew stronger, the activity in most of those regions fell off rapidly, until just a handful remained lit up on the images.
The finding that the regions active during craving were also lit up during euphoria suggests that the human brain does not have a dedicated "craving center" of the sort that researchers had been searching for in animals. But most startling to the researchers was the finding that a particular region linked with feelings of pleasure or euphoria, the nucleus accumbens, was more strongly associated with the sensation of craving.
The work "points the way toward far more sophisticated targets for addiction treatments," says Alan Leshner, director of the National Institute on Drug Abuse. Such treatments might be aimed at combating a particular aspect of a drug experience--euphoria, craving, or withdrawal, depending on an addict's needs--by suppressing activity in particular brain regions. "There might not be [just] one treatment for drug addiction," adds Hyman, who now directs the National Institute of Mental Health.
[See the 3 October  issue of Science for a special issue on "The Science of Substance Abuse."]