Addiction: Hijacking
the Brain Brain images for (11C)d threo-methylphenidate, which show the concentration of dopamine transporters in a control and in a methamphetamine abuser tested 80 days after detoxification. The abuser shows a much lower concentration than the control. "These studies provide some of the first clear evidence that methamphetamine at dose levels taken by human abusers leads to dopamine transporter reduction," said Brookhaven psychiatrist Nora Volkow, lead investigator on the study. "For the first time we can also see that this transporter reduction is associated with motor and cognitive impairment." Previously, in animal studies and two small human studies, researchers documented reductions in dopamine transporters. Past studies did not test whether these reductions were associated with changes in cognitive and motor function. "We also have the first evidence that methamphetamine affects circuits of the brain other than those regulated by dopamine, and that the drug causes changes that are consistent with inflammation throughout the brain," Volkow continued. "This is objective evidence that methamphetamine is damaging to the brain. These changes are much greater than what we have seen with heroin, alcohol, or cocaine. We need to further study whether these changes are long-lasting and result in long-term impairment of memory and motor functions, such as motor speed and motor coordination."
Each study volunteer was given an injection called a radiotracer, a radioactive chemical "tag" designed to bind to dopamine transporters in the brain. The researchers then scanned the subjects' brains using a positron emission tomography (PET) camera. The PET camera picks up the radioactive signal of the tracer and shows where it is bound to dopamine transporters. The strength of the signal indicates the number of transporters. Within two weeks of the PET scans, the researchers administered a battery of neuropsychological tests. These included tests of fine and gross motor function and tests of attention and memory. Methamphetamine abusers showed a significant reduction in dopamine transporters in the caudate (27.8%) and putamen (21.1.%) - two areas of the striatum, a section of the brain that controls movement, attention, motivation, and other higher functions -- compared with non-abusers in the study. The reduction was evident even in abusers who had been detoxified for 11 months or more. Study subjects with reduced dopamine transporters also exhibited memory impairment and slowed motor function.
"This finding was a complete surprise," Volkow says. "Most drug studies have shown decreased metabolism. The increased metabolism we saw is consistent with an inflammatory response. This result, taken together with our other findings, indicates that this is a very toxic drug." The presence of inflammation signals that there is a physical insult to the brain.
Methamphetamine is a highly addictive stimulant that dramatically affects the central nervous system. Long reported as a dominant drug problem in southern California, methamphetamine abuse has recently become a substantial problem in other areas of the West and Southwest as well. Usage has also recently increased in areas of the Midwest and South. According to a survey by the National Institute on Drug Abuse, an estimated 4.9 million Americans have tried methamphetamine at some point in their lives. Brookhaven scientists have done extensive research on addiction. Studies by Dr. Volkow and colleagues have shown that dopamine plays an important role in addiction to cocaine, nicotine, alcohol, heroin, and other drugs. Previous research at Brookhaven has shown that addictive drugs increase the level of dopamine in the brain while the subject is intoxicated, and that addicts have fewer dopamine receptors than non-addicts. This study was funded by the U.S. Department of Energy; the National Institute on Drug Abuse, part of the National Institutes of Health; the Office of National Drug Control Policy; and the General Clinical Research Center at University Hospital Stony Brook. It was done in collaboration with researchers from the State University of New York at Stony Brook and the University of California, Los Angeles. The full text of these studies will appear on the American Journal of Psychiatry web site at: http://ajp.psychiatryonline.org.
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