Cocaine May Play Role in User's Depression

Many long-time cocaine users suffer from depression. The rates of depression reported in chronic cocaine abusers are significantly higher than in the general population.

Trying to determine why cocaine users experience depression and other disorders, scientists believe it is linked to the damage that the drug does to the very brain cells that make users feel high when they do cocaine.

Damaging or actually killing off the brain cells that help the user feel pleasure could account for the high rates of depression among chronic cocaine abusers, the researchers said.

When cocaine is used it increases the level of dopamine in the brain, creating the high that users feel, but prolonged use of the drug reduces the dopamine levels, making it harder for the user to experience positive feelings.

"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 University of Michigan Medical School and chief of the Ann Arbor Veterans Affairs Medical Center 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 colleagues studied samples of brain tissue obtained during autopsies of 35 long-term cocaine users and 35 non-users. They analyzed the tissue for dopamine and the protein VMAT2, which is found in dopamine transporters.

Urine or serum samples were also analyzed for the presence of cocaine, opioids, antidepressants, and antipsychotic medications. A person close to each individual was interviewed about the individual's substance abuse, alcoholism, and symptoms of personality and mood disorders.

Researchers found that cocaine users had lower concentrations of dopamine and VMAT2 in their brains than did non-users. Additionally, cocaine users suffering from depression had lower levels of VMAT2 than those who were not depressed.

"Our data provide a very good biochemical basis for cocaine withdrawal symptoms. The existing literature shows that a depressed cocaine user is going to have more problems maintaining family and work, have a harder time quitting, is more likely to drop out of treatment, and is more likely to commit suicide," Little said.

Little and colleagues were uncertain whether dopamine cells had been destroyed or just dysregulated by cocaine use, and if such changes could be reversed.

"We could be seeing the result of the brain's attempt to regulate the dopamine system in response to cocaine use, to try to reduce the amount of dopamine that's released by reducing the ability to collect it in vesicles," Little said. "But we could also be seeing real damage or death to dopamine neurons. Either way, this highlights the fragility of these neurons and shows the vicious cycle that cocaine use can create."

Further efforts at clarifying the detrimental effects of cocaine on brain cells may help in the development of effective treatment interventions and pharmacotherapies, the researchers suggested.

The study was funded in part by the National Institute on Drug Abuse.