ENZYME SEEN IN COCAINE STUDY

An enzyme identified in the brains of animals fed continuous
doses of cocaine could be involved with the addiction process,
according to scientists at Rockefeller University in Manhattan. The
finding could ultimately lead to a better understanding of drug abuse
and to the development of new medicines to treat drug addiction.

James Bibb, working with Paul Greengard, a recent recipient of the
Nobel Prize in Physiology or Medicine, discovered the increased levels
of the enzyme, which is a brain protein called cyclin-dependent kinase
5, or Cdk5, in animals repeatedly exposed to cocaine. Chronic cocaine
exposure led to changes in gene expression and the altered levels of
Cdk5. This protein is a kinase, or signaling molecule, that regulates
the action of dopamine. Dopamine, a neurotransmitter, is the key
player in the brain's pleasure pathway.

Blocking this signaling system, the Rockefeller scientists showed in a
recent study, had a major impact on the animal's behavior. The mice
almost doubled their activity level, suggesting that Cdk5's role in
the brain directly targets the dopamine system. Dopamine has been
implicated in fine motor control, mood and reproductive behavior.

Bibb and his colleagues suspect that Cdk5 may be part of the body's
biological response to block the effects of cocaine. The increased
levels of the kinase dampen the brain's response to subsequent
exposures to the cocaine. This pathway could be critical in trying to
understand why chronic users require increased amounts of the drug to
obtain the same high. The study was published in Nature on March 16.

The hope is to find a treatment to block cocaine craving in much the
same way that methadone is used as a treatment for heroin addiction.

"It seems as if the body is trying to protect itself" through this
pathway, says Rockefeller's Greengard. Figuring out how to alter this
pathway to block drug addiction will not be easy, he added. Another
scientist in the study, Angus Nairn, said that Cdk5 has many functions
in the brain, and a medicine would have to selectively block the
dopamine pathway involved in addiction. The group will now test the
role, if any, of Cdk5 in other drugs of abuse-alcohol, nicotine,
marijuana and LSD.

"If the same process is occurring in humans, people who abuse drugs
have altered their brain's normal dopamine system," Nairn said.
Perhaps an inhibitor of Cdk5 would help normalize the dopamine system
in addicts trying to stop using cocaine.