Real-time monitoring of brain activity helps explain how cues contribute to drug relapse

Real-time monitoring of dopamine activity in the brain shows that in rats the mere anticipation of receiving cocaine may cause significant increases in dopamine levels. This finding may help explain why, in humans recovering from cocaine addiction, cocaine paraphernalia, surroundings, and other factors associated with drug use can elicit an intense craving for the drug, often resulting in relapse to use. Dopamine is a brain chemical associated with feelings of pleasure (reward); increases in dopamine levels in an area of the brain called the nucleus accumbens have been associated with drug use. Measuring dopamine level changes in real time enable researchers to carefully and accurately correlate drug-related behaviors in rats with changes in brain chemistry.

The researchers trained male rats to self-administer cocaine by pressing a lever and to associate the availability of cocaine with certain cues such as changes in lighting and an auditory tone. During daily sessions, the rats had access to cocaine and their behavior was recorded. Using fast-scan cyclic voltammetry, the researchers monitored changes in dopamine levels in the nucleus accumbens of the rats every 100 milliseconds while the rats had access to cocaine or were exposed to drug-related cues. Voltammetry allows subsecond measurements of dopamine release by monitoring changes in electrochemical currents that occur when brain cells release dopamine.

In the seconds following the cues, but before rats pressed the lever to receive cocaine, researchers observed an increase in dopamine in rats' brains. After each lever press, an additional increase in dopamine was measured.

In another experiment, the researchers found that they could initiate drug-seeking behaviors in rats by stimulating the release of dopamine in the nucleus accumbens.

WHAT IT MEANS: These findings reveal for the first time that rapid dopamine transmission occurs during key components of cocaine-seeking behavior and during presentation of cocaine-associated stimuli. Rather than a pharmacological effect, dopamine increases in response to cues that have a learned association with cocaine.

This study, published by Dr. Regina Carelli and colleagues from the University of North Carolina at Chapel Hill and funded by the National Institute on Drug Abuse, appeared in the April 10 issue of Nature.

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