Vaccine triggers cocaine mop-up in rats.

For all the millions of dollars spent to find a way to halt cocaine abuse, physicians still lack a useful medicine to break the drug's addictive power. The exact site and chemistry of addiction remain a puzzle. Moreover, many of the brain pathways influenced by cocaine coincide with paths essential to normal function, so targeting one can knock out the other.

Now, researchers report that they can mop up cocaine in the bloodstream of rats before it reaches the brain.

Scientists at the Scripps Research Institute in La Jolla, Calif., have developed a vaccine that calls up antibodies against the drug, resulting in antibody-cocaine complexes too unwieldy to enter the rats' brains. Cocaine itself rarely sparks an immune reaction. But by linking the part of cocaine that antibodies recognize to a molecule that triggers antibody production, the researchers made a vaccine that halves the concentration of free cocaine in the rats' blood.

Cocaine in the brain drops accordingly.

In the study, published in the Dec. 14 Nature, scientists injected rats with the experimental vaccine or with a form missing the cocaine component. Next, they gave the animals a dose of cocaine. Animals in the first group had 77 percent less cocaine in the cerebellum-a site of the drug's action-than the controls did.

"Blocking cocaine by keeping it outside the brain should have fewer side effects than manipulating the way it behaves at specific nerve sites inside," says Scripps researcher George F. Koob. Drugs that work in the brain can stop people from taking cocaine, he explains, but they also make people unable to move.

The researchers observed the rats' behavior to determine whether cocaine had reached the brain. Rats on cocaine typically can't keep still; they engage in various repetitive movements-episodes of sniffing, for example. These behaviors lessened greatly in the vaccinated rats. New experiments, Koob says, will highlight the vaccine's effect on more crucial addictive behavior, in which the rats repeatedly press a bar to get the drug.

The vaccine also appears to be highly specific. It does not prevent the effects of amphetamines, another type of stimulant.

A similar vaccine to treat addiction in people remains distant. For one thing, the particular antibody-stimulating part of the vaccine, which comes from marine limpets, may do too good a job. "We'd need to rule out potential autoimmune problems," says Koob.

"I see a possible place for a vaccine with people who want to get off the drug, who are highly motivated but tempted," says Koob. Heroin addicts determined to kick the habit need constant monitoring to stay on drugs that block heroin's pleasurable effects, says George Uhl of the National Institute on Drug Abuse's Baltimore laboratories. A vaccine might reduce the need for monitoring.

"I don't think you'd ever grab people using crack cocaine off the street, immunize them, and expect this is going to work," says Koob. Psychiatrist David W. Self of Yale University School of Medicine agrees. Vaccination, he says, does not target the basic process of addiction in those already addicted.

Koob suggests that a vaccine may someday serve as an adjunct to behavior-shaping therapy and drugs. "It would put up a significant barrier for cocaine."