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MAPPING THE ROOT OF COCAINE CRAVING:

SURPRISING FINDINGS ON DRUG'S EFFECT IN BRAIN REGIONS

UPTON, NY - The part of the brain that is abnormal in some people with obsessive-compulsive disorder may also play a key role in craving and abuse of cocaine. And, drug craving is associated more with the right side of the brain than the left.

These new results, and other information about the brain regions affected by cocaine, are being published today in the American Journal of Psychiatry by scientists from the U.S. Department of Energy's Brookhaven National Laboratory, the School of Medicine of the State University of New York at Stony Brook, and New York University.

"In this study, we have used a powerful brain-imaging technique to map important information about frontal-lobe regions associated with cocaine's effects," said Nora Volkow, leader of the team and chair of Brookhaven's Medical Department. "Some of our findings are surprising, and will help guide us and our colleagues in future studies of how drugs affect the brain, and in designing treatments for addiction."

The study involved multiple brain scans of 20 cocaine addicts, made using positron emission tomography (PET) at Brookhaven's Center for Imaging and Neurosciences. The patients received an intravenous injection of methylphenidate - commonly known as Ritalin - which acts on the same brain pathway as cocaine.

The researchers found that the cocaine addicted subjects reported feeling a craving for cocaine that corresponded directly with Ritalin's stimulation of the brain regions known as the right striatum and right orbitofrontal cortex.

It is the first time that the ability of Ritalin to induce craving in cocaine addicts was associated with an activation of these brain regions, which the investigators has previously found to be active in cocaine abusers who spontaneously complained of suffering from intense craving.

It is also the first time that the right side of the brain has been specifically associated with these drug responses, a finding that is in line with the notion that the right side of the brain is involved with emotional responses while the left is associated with more cognitive activities.

The striatum and the orbitofrontal cortex, which are linked to one another, are associated with normal response to stimuli, but have also been found to be abnormal in some people with obsessive-compulsive disorder. The association of craving with these areas, Volkow said, "may be a clue to the loss of control and compulsive drug-taking behavior that cocaine addicts experience."

Also among the surprising findings was the discovery that an increase in the key brain chemical dopamine, which is important in mediating pleasurable responses to drugs, was not sufficient by itself to be enough to boost activity in the frontal regions of addicts' brains.

Moreover, Volkow said, the effects of dopamine in the brain varied markedly among the subjects. Part of the differences in their responses were due to the concentration of dopamine receptors, the molecules that transmit the dopamine's signal.

"The differences in the concentration of these receptors, which are likely to be regulated in part by genetic factors, provide a mechanism to understand the differences in responses to drugs among people, and may help us understand issues such as vulnerability to drug addiction," Volkow said.

Along with Volkow, the study's authors were Brookhaven's Gene-Jack Wang, Joanna Fowler, Samuel Gatley, Jean Logan, Yu-Shin Ding and Naomi Pappas; SUNY Stony Brook's Robert Hitzemann; and Burton Angrist, recently retired from NYU.

The research was sponsored by DOE's Office of Science, and by the National Institute on Drug Abuse, one of the National Institutes of Health.

The U.S. Department of Energy's Brookhaven National Laboratory creates and operates major facilities available to university, industrial and government personnel for basic and applied research in the physical, biomedical and environmental sciences, and in selected energy technologies. The Laboratory is operated by Brookhaven Science Associates, a not-for -profit research management company, under contract with the U.S. Department of Energy.

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