UPTON, NY -- A new brain-imaging study at the U.S. Department of Energy's Brookhaven National Laboratory indicates that some of the damage caused by methamphetamine -- a drug abused by ever-increasing numbers of Americans -- can be reversed by prolonged abstinence from the drug. The results appear in the December 1, 2001 issue of The Journal of Neuroscience.
"Methamphetamine is a particularly problematic, highly addictive drug," said Nora Volkow, who led the study with Linda Chang. Their team had previously shown that methamphetamine abusers have significantly depleted levels of dopamine transporters. These proteins, found on the terminals of some brain cells, recycle dopamine, a brain chemical associated with pleasure and reward and also essential for movement. The study also found that meth abusers had impaired cognitive and motor function (see http://www.
"These changes could mean that meth abusers would be predisposed to such neurodegenera-tive disorders as Parkinson's disease, which is also characterized by problems with dopamine and motor function," Volkow said. "It depends in part on whether the damage is reversible."
To help answer this question, Volkow and her team used positron emission tomography, or PET scanning, to measure the level of dopamine transporters in methamphetamine abusers after varying periods of abstinence. One group of 12 methamphetamine abusers was scanned within 6 months of taking the drug, and, for 5 of these subjects who managed to stay drug-free, the scan was repeated after 9 months of abstinence. Another group of 5 methamphetamine abusers was studied only after 9 months of abstinence. All subjects were compared with normal controls.
For each scan, each study volunteer was given an injection carrying a radiotracer, a radioactive chemical "tag" designed to bind to dopamine transporters in the brain. The researchers then scanned the subjects' brains using a PET camera, which picks up the radioactive signal of the tracer bound to the transporters. The strength of the signal indicates the number of transporters.
The scientists also looked for improvements in cognitive and motor function after abstinence by administering a battery of neuropsychological tests. These included tests of fine and gross motor function and tests of attention and memory.
The main finding was that, in methamphetamine abusers who were able to stay drug-free for at least 9 months, dopamine transporter levels showed significant improvement, approaching the level observed in control subjects. In abusers studied within 6 and after 9 months, the longer the period between the first and second evaluation, the larger the increase in dopamine transporter levels. Cognitive and motor function showed a trend toward improvement on some tests, but these changes were not statistically significant.
"The increase in dopamine transporter levels with prolonged abstinence indicates that the terminals of dopamine-secreting cells, which are thought to be damaged by methamphetamine abuse, are able to regenerate," Volkow said. Another possibility is that other, undamaged terminals are able to branch out and make up for the loss.
"These findings have implications for the treatment of methamphetamine abusers because they suggest that protracted abstinence and proper rehabilitation may reverse some of the meth-induced alterations in dopamine cells," Volkow said. "Unfortunately, we did not see a parallel improvement in function."
The recovery of dopamine transporters may not have been sufficient to completely make up for the damage to the dopamine terminals, she suggested. Additionally, other systems necessary for neuropsychological function might also be damaged by the drug -- and less able to recover. Also, Volkow noted, the sample sizes were small. "Further study in larger samples is required to assess whether recovery of dopamine transporters with protracted abstinence is associated with recovery of neuropsychological function," she said.
This work was funded by the U.S. Department of Energy, which supports basic research in a variety of scientific fields; the National Institute on Drug Abuse; the National Institutes of Health; and the Office of National Drug Control Policy.
The U.S. Department of Energy's Brookhaven National Laboratory (http://www.
Note to local editors: Nora Volkow lives in Shoreham, New York.