Study suggests cocaine impairs `pleasure circuits'; may explain users' higher depression rates

Wednesday, January 1st 2003, 12:00 am

By: News On 6

NEW YORK (AP) _ Chronic cocaine use harms brain circuits that help produce the sense of pleasure, which may help explain why cocaine addicts have a higher rate of depression, a study suggests.

It's not clear whether cocaine kills brain cells or merely impairs them, or whether the effect is reversible, said study author Dr. Karley Little. But it's bad news for cocaine addicts in any case, he said.

``I personally wouldn't want to lose 10 or 20 percent of my reward-pleasure center neurons, or have them just deranged or not working right,'' said Little, of the Ann Arbor, Mich., Veterans Affairs Medical Center and the University of Michigan.

He and colleagues studied brain samples taken during autopsies from long-term, heavy cocaine users. Their results were reported in the January issue of the American Journal of Psychiatry.

Little said the research did not reveal whether the brain impairment resulted from years of use or just recent use before death.

Stephen Kish, head of the human brain laboratory at the Center for Addiction and Mental Health in Toronto, said researchers have ``always considered cocaine to be a dangerous drug'' because of its potential for addiction and harm to the heart.

``We now have to add to the list (of risks) a damaging effect of cocaine on the brain, which was something we never expected before,'' Kish said.

The research provides ``a piece of the puzzle'' in explaining why cocaine users run a higher risk of depression, said Dr. Deborah Mash, a neuroscientist at the University of Miami School of Medicine.

It remains unclear whether cocaine causes depression or whether people start using the drug because they are depressed. But in either case, Mash said, the study suggests brain changes could ``light the fuse'' for depression in a cocaine user who is prone to it.

The study also suggests that the brain changes could cause the depression commonly seen during cocaine withdrawal, Mash said.

In the study, Little and colleagues studied brain autopsy specimens from an area called the striatum in 35 cocaine users and 35 non-users of similar age and sex.

They measured levels of a protein called VMAT2, which is found in brain cells that signal each other with a chemical called dopamine. Dopamine neurons form circuits that are critical for the brain to feel pleasure.

The study found that cocaine users' VMAT2 levels were lower on average. That could mean dopamine neurons had been damaged or killed _ an effect not observed in animal studies _ or that they were making less VMAT2, which suggests they also were making less dopamine, Little said.

A person with impaired or missing dopamine neurons could have difficulty feeling pleasure and might become depressed, said Little, who added that researchers will now compare the number of dopamine neurons in the autopsy specimens.

The study found hints that VMAT2 levels were lower in cocaine users with severe depression than in other users, but statistical analysis suggested this could be a coincidence. Little said the link is strengthened when other data are taken into account.