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Chronic Cocaine Use Damages Dopamine Neurons

URL: http://www.mapinc.org/drugnews/v04/n580/a05.html
Newshawk: CMAP ( http://www.mapinc.org/cmap )
Pubdate: Tue, 13 Apr 2004
Source: Medical Post (Canada)
Copyright: 2004 The Medical Post
Contact: medpost@rmpublishing.com
Website: http://www.medicalpost.com/
Details: http://www.mapinc.org/media/3180
Author: David Milne

CHRONIC COCAINE USE DAMAGES DOPAMINE NEURONS

ANN ARBOR, MICH. Analysis here of postmortem brain tissue provides more evidence that chronic cocaine use reduces striatal levels of vesicular mono-amine transporter protein ( VMAT2 ) and results in dopamine neuronal changes related to disordered mood.

"This is the clearest evidence to date that cocaine dependency results in deleterious changes in dopamine neurons," Dr. Karley Little, chief of the Ann Arbor VA Medical Centre's Affective Neuropharmacology Laboratory and associate professor of psychiatry at the University of Michigan medical school, said during an interview.

Dr. Little and colleagues assessed the integrity of the dopamine system in brain tissue from 35 known cocaine users and 35 non-users matched for age, sex, race and cause of death.

Using tissue from the striatum, an area of the brain with the highest concentration of dopamine neurons, they measured the level of VMAT2 ( a protein that pumps dopamine molecules into storage vesicles ), VMAT2's binding availability to a selective radiotracer molecule ( another assessment of VMAT2 presence and activity ) and the overall dopamine level to find how much was available at the time of death.

They found all three levels were lower in cocaine users than in non-users. Levels tended to be lowest in cocaine users who were diagnosed as having cocaine-induced mood disorders at the time of their deaths.

It has been known that immediately after cocaine exposure, synaptic dopamine increases, an event believed to be critical in causing the pleasurable experience associated with cocaine intake. This study illuminates the molecular mechanisms responsible for the withdrawal symptoms and sustained depression that some cocaine users experience after chronic use.A

Other researchers have found that those individuals who experience not only pleasure from cocaine use but also "punishment" by its withdrawal, by persistent depression and by dysthymic and suicidal feelings, are those whose addiction is most disruptive and difficult to treat.A

Traditionally, cocaine use has not been associated with the intense physical dependence that is seen with alcohol and narcotics.A But the clinical literature does indicate that cocaine users have withdrawal symptoms—which vary a lot between individuals, from mild to intense. About a third feel markedly depressed, listless, anxious and uncomfortable.A

It has become clear that people who have those symptoms are likely to become more dependent on the drug and find it harder to quit.

The study appeared in the American Journal of Psychiatry.