Scientists at The Scripps Research Institute have discovered therole of a new class of brain receptors in cocaine abuse, a findingthat could enhance approaches to addiction and perhaps shedlight on such psychiatric disorders as mania and depression.

Studies in rats revealed that compounds that block one of fivedopamine receptors believed to be a part of the brain's"pleasure center," D-3, cause the animals to reduce by up to 60percent the amount of cocaine they self-administer.

"However," cautioned study author S. Barak Caine, "we stilldon't know whether these D-3 selective drugs can reducesymptoms of craving and withdrawal." His results werepublished with co-author George Koob of Scripps'neuropharmacology department in Friday's issue of the journalScience.

Overwhelming evidence suggests that cocaine produces itsbehavioral effects by increasing the activity of dopamine, aneurotransmitter whose receptors are thought to regulate brainactivities related to movement, motivation, and perhapsemotions and other thought processes.

The D-3 receptor, recently cloned by French scientists Jean-Charles Schwartz and Daniel Levesque, appears concentrated inthe limbic system of the brain that mediates emotion andbehavior, rather than in parts responsible for motor control,where long-studied D-1 and D-2 receptors predominate.

Approaching addiction with compounds that bind selectively toD-3 receptors rather than D-2 receptors, therefore, may reducethe potential for side effects on motor function.

Past attempts to lessen cravings for cocaine by laboratory ratsusing dopamine antagonists have tended to end in increasedcocaine intake, presumably to compensate for the antagonist'seffects.

In people, dopamine antagonists also seem to exacerbatesymptoms of depression and craving, Caine said.

"What we're interested in achieving," he said, "is a means ofregulating the dopamine system and by so doing, findingcompounds that reduce these symptoms without producingdependence on the compounds themselves."

In the study, rats connected to intravenous tubes were allowedto administer as much cocaine as they wanted for three hours aday, a limit that quickly leads to a stable baseline, with eachrat taking almost exactly the same amount each day. When therats self-administered cocaine in combination with very smallquanities of drugs that bind to the D-3 receptor, they took "upto 60 percent less than their normal daily amount," Caine said.

-- Nancy Garcia Associate Editor

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