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ANALYTICAL CURRENTS Dual role for dopamine in addiction It didn’t take long for researchers to notice that dopamine plays a role in drug addiction, but the details haven’t been as easy to pinpoint. Now, Regina Carelli, Mark Wightman, and colleagues at the University of North Carolina–Chapel Hill have found that dopamine acts in two crucial ways: It is released before cocaine use, initiating drug-seeking behavior, and after cocaine use, possibly as a reward that reinforces the behavior. Furthermore, dopamine is released in response to environmental cues that are associated with cocaine use, even when the drug isn’t present. Many previous studies using rats to model human addiction have measured increases in the tonic levels of dopamine— that is, minute-to-minute changes—in a region of the brain called the nucleus accumbens, which is rich in dopamine terminals. This time, the researchers used fast-scan cyclic voltammetry to measure phasic, or subsecond, dopamine release. The rats had been trained to press a lever to administer a dose of cocaine to themselves. Before they approached the lever, they executed behavioral rituals that the researchers characterized as
drug-seeking behavior. Taking measurements every 100 ms, the researchers observed a modest yet reproducible transient increase in extracellular dopamine before the rats began the final approach to the lever, suggesting that dopamine Figure Not Available primes the drug-seeking befor Use on the Web havior. A larger increase followed administration of the drug. When direct, periodic stimulation was applied to dopamine cells that innervate the nucleus accumbens, the rats pressed the lever in synchrony with the stimulation. in rats who were never trained to associThe researchers also trained some ate the cue with the drug.) rats to associate an audiovisual cue with There are some subtleties here. For excocaine administration. Presenting the ample, subsecond dopamine release may cue was meant to be analogous to a be inhibited if the tonic levels are high. human addict seeing drug paraphernaBut the overall message is that the dopalia, a situation that elicits intense drug mine is critically involved in drug-seeking cravings. In this case, dopamine was released in response to the cue, even if the behavior, rather than simply being released in response to the drug, the researchers drug was not subsequently adminissay. (Nature, 2003, 422, 614–618) tered. (There was no dopamine release
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