ANN ARBOR, MI New research results strongly suggest that cocaine bites the hand that feeds it, in essence, by harming or even killing the very brain cells that trigger the "high" that cocaine users feel.

This first-ever direct finding of cocaine-induced damage to key cells in the human brain's dopamine "pleasure center" may help explain many aspects of cocaine addiction, and perhaps aid the development of anti-addiction drugs. It also could help scientists understand other disorders involving the same brain cells, including depression.

The results are the latest from research involving postmortem brain tissue samples from cocaine abusers and control subjects, performed at the University of Michigan Health System and the VA Ann Arbor Healthcare System. The paper will appear in the January issue of the American Journal of Psychiatry.

"This is the clearest evidence to date that the specific neurons cocaine interacts with don't like it and are disturbed by the drug's effects," says Karley Little, M.D., associate professor of psychiatry at the U-M Medical School and chief of the VAHS Affective Neuropharmacology Laboratory. "The questions we now face are: Are the cells dormant or damaged, is the effect reversible or permanent, and is it preventable?"

Little and his colleagues report results from 35 known cocaine abusers and 35 non-drug users of about the same age, sex, race and causes of death. Using brain samples normally removed during autopsy, the researchers measured several indicators of the health of the subjects' dopamine brain cells, which release a pleasure-signaling chemical called dopamine. The cells interact directly with cocaine.

The team looked at levels of a protein called VMAT2, as well as VMAT2's binding to a selective radiotracer molecule, and overall dopamine level.

In all three, cocaine users' levels were signif
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Contact: Kara Gavin
umhsmedia@umich.edu
734-764-2220
University of Michigan Health System
1-Jan-2003