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Researchers Find Trigger for Cocaine Addiction

February 16, 2006

Discovery could lead to new treatments, researchers say

Experiments in rats have linked the craving for cocaine to a specific molecule that appears to train the brain to crave the drug.

The finding could lead to addiction treatments that would block this biologic trigger, experts say.

The researchers found that a protein, called orexin A, acts on an area of the brain that is key to priming the brain for addictive drugs. In experiments with rats, they show that orexin A causes an adaptation that is needed for the development of behavior associated with drug craving in human addicts.

The findings appear in the Feb. 16 issue of Neuron.

“We have looked at the protein orexin A, and found that it causes plasticity in an area of the brain that has been shown to be involved in reward behaviors,” said study author Stephanie L. Borgland, a researcher at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco.

This area of the brain has been found to be activated when animals prefer morphine, Borgland said. “Our paper is actually showing the mechanism of how that happens,” she added.

Borgland’s team based their experiments on past studies that found that orexins are important regulatory proteins produced in the brain’s lateral hypothalamus. It has been known that orexins activate an area in the brain called the ventral tegmental area (VTA), which is a critical site of brain adaptation caused by addictive drugs.

In their experiments, Borgland’s group demonstrated that orexin A increases the activity of neurons in the VTA associated with such plasticity. In addition, they found that orexin A was needed for “behavioral sensitization” to cocaine. This was shown as an increase in activity by the animals when they received the drug and even after the drug was withdrawn. This indicates that the animals experienced an increased craving for the drug, Borgland said.

“This gives us a better understanding of a pathway that’s involved in addiction,” Borgland said. “It may provide a new target for developing anti-craving medications.”

One expert believes this finding may have therapeutic implications.

“The finding is consistent with other work in addiction focusing on processes that project onto the dopaminergic pathways, either upstream or downstream,” said Steven Shoptaw, a research psychologist at the Integrated Substance Abuse Programs at the University of California, Los Angeles.

“The finding is an exciting development, and provides compelling support for the working thesis that a critical basis for addiction lies within neurobiology,” Shoptaw said. “There is plenty of evidence here to move forward the idea that orexin receptors represent novel targets for developing new medications that are intended to treat addiction.”

Another expert agrees that drugs that block orexin might be effective in treating drug addiction.

“Antagonist of orexin looks like a very exciting tool,” said Dr. Thomas Kosten, a professor of psychiatry at Yale University Medical School.

If these behaviors are changed in animals, then these drugs can be tried on people, he said.

“Human studies would determine whether this type of medication might reduce cocaine euphoria, craving or other subjective effects associated with addiction and relapse,” Kosten said. “This work is clearly approaching a finding that would excite the community of clinical researchers in addiction.”

More information

The National Institute on Drug Abuse can tell you more about cocaine addiction (www.nida.nih.gov ).




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