Discovery of a 'drug anticipation' brain signal

In studies with rats, researchers have distinguished a burst of the brain chemical dopamine from a reward-related brain region that is associated with anticipating the delivery of cocaine. The finding, publishing in the May 19 issue of Neuron, reveals the brain signal that likely underlies the fundamental motivation to obtain such drugs, said the scientists. Thus, the finding may give clues to the basic brain mechanism that causes drug-seeking behavior, they said.

In their experiments, researchers led by Regina M. Carelli of the University of North Carolina in Chapel Hill used infinitesimally small recording electrodes in the brains of rats to detect the release of the neurotransmitter dopamine from the region called the nucleus accumbens. Almost all drugs of abuse cause release of dopamine from this region--part of the brain's reward system. Such release triggers neurons in other brain regions, generating the pleasurable sensation associated with taking such drugs.

The researchers first taught rats to self-administer cocaine by pressing a lever when a light in their cage came on. They next extinguished this behavior by substituting saline solution for the cocaine. Finally, they reinstated the lever-pressing behavior by restoring the cocaine.

Their measurements revealed three distinct types of transient bursts of dopamine from the nucleus accumbens. One dopamine signal that occurred immediately before a lever press continued to occur, even after the rats ceased to receive cocaine. This signal, concluded the researchers, could reflect the motivation to obtain the drug.

However, another dopamine signal that occurred immediately after the lever press declined rapidly after the cocaine ceased. This signal could encode the learned association between environmental cues and cocaine, theorized the researchers. A third spontaneous signal, unlike the second type, was associated with the levels of cocaine in the rats' systems. This signal could function to activate brain networks associated with the pleasurable effects of cocaine, wrote the researchers.

"These results show that dopamine release transients involved in different aspects of cocaine administration are highly plastic--differentially governed by motivation, leaned association linked with environmental stimuli, and the pharmacological actions of cocaine," the researchers concluded.

The researchers include Garret D. Stuber, R. Mark Wightman, and Regina M. Carelli of the University of North Carolina at Chapel Hill. This work was supported by grants from the National Institute on Drug Abuse.

Stuber, G.D., Wightman, R.M., and Carelli, R.M. (2005). Extinction of Cocaine Self-Administration Reveals Functionally and Temporally Distinct Dopaminergic Signals in the Nucleus Accumbens. Neuron 46, 661-669. www.neuron.org

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