Single cocaine exposure boosts both drug craving and avoidance

A single exposure to cocaine activates different brain systems that can enhance both the pleasurable and unpleasant effects of psychoactive drugs, according to new research studies with rats. The dual effect may explain why some people become addicted to drugs while others do not, the scientists say. It appears to result from cocaine's effect on two parallel, but opposing brain circuits.

In some people, the two opposing processes may develop at different rates, and if the drug-aversion circuitry predominates, it may protect some individuals from becoming addicted to drugs of abuse, said Howard Fields, MD, PhD, UCSF professor of neurology and physiology. Fields is Director of the Wheeler Center for the Neurobiology of Addiction and an investigator in UCSF's Ernest Gallo Clinic and Research Center where the study was carried out. Identifying what accounts for the opposing actions of the two brain circuits could lead to medicines that treat addiction by changing the balance between the two pathways -- strengthening the drug-aversion response and, in effect, weakening its addictive potential, Fields said. Different neurotransmitters may act in the two circuits and would be likely targets for such treatment, he said.

The study is being published online the week of March 29 by the Proceedings of the National Academy of Sciences (PNAS). Fields is senior author of the paper.

Fields and his colleagues used a drug to block activity in the ventral tegmental area of the brain, or VTA, where dopamine neurons have been shown to be active in learning and memory processes involved in addiction. The drug blocked cocaine's ability to boost morphine's rewarding effect, as well as cocaine's enhancement of an unpleasant effect of another drug, demonstrating that the two opposing brain circuits involve the VTA.

The study involved "place conditioning," in which the animals are allowed to express either an attraction or aversion to two differently colored an

Contact: Wallace Ravven
University of California - San Francisco

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