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.