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The Journal of Neuroscience, June 14, 2006, 26(24):6583-6588; doi:10.1523/JNEUROSCI.1544-06.2006

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Brief Communications
Cocaine Cues and Dopamine in Dorsal Striatum: Mechanism of Craving in Cocaine Addiction

Nora D. Volkow,¹ Gene-Jack Wang,² Frank Telang,¹ Joanna S. Fowler,³ Jean Logan,³ Anna-Rose Childress,⁴ Millard Jayne,¹ Yeming Ma,¹ and Christopher Wong³

¹National Institute on Alcohol Abuse and Alcoholism, Bethesda Maryland 20892, ²Medical Department and ³Department of Chemistry, Brookhaven National Laboratory, Upton, New York 11973, and ⁴Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Correspondence should be addressed to Dr. Nora D Volkow, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5274, Bethesda, MD 20892. Email: nvolkow{at}nida.nih.gov

The ability of drugs of abuse to increase dopamine in nucleus accumbens underlies their reinforcing effects. However, preclinical studies have shown that with repeated drug exposure neutral stimuli paired with the drug (conditioned stimuli) start to increase dopamine by themselves, which is an effect that could underlie drug-seeking behavior. Here we test whether dopamine increases occur to conditioned stimuli in human subjects addicted to cocaine and whether this is associated with drug craving. We tested eighteen cocaine-addicted subjects using positron emission tomography and [¹¹C]raclopride (dopamine D₂ receptor radioligand sensitive to competition with endogenous dopamine). We measured changes in dopamine by comparing the specific binding of [¹¹C]raclopride when subjects watched a neutral video (nature scenes) versus when they watched a cocaine-cue video (scenes of subjects smoking cocaine). The specific binding of [¹¹C]raclopride in dorsal (caudate and putamen) but not in ventral striatum (in which nucleus accumbens is located) was significantly reduced in the cocaine-cue condition and the magnitude of this reduction correlated with self-reports of craving. Moreover, subjects with the highest scores on measures of withdrawal symptoms and of addiction severity that have been shown to predict treatment outcomes, had the largest dopamine changes in dorsal striatum. This provides evidence that dopamine in the dorsal striatum (region implicated in habit learning and in action initiation) is involved with craving and is a fundamental component of addiction. Because craving is a key contributor to relapse, strategies aimed at inhibiting dopamine increases from conditioned responses are likely to be therapeutically beneficial in cocaine addiction.

Key words: imaging; raclopride; addiction; caudate; putamen; conditioned responses; D₂ receptors

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Received April 10, 2006; revised May 8, 2006; accepted May 14, 2006.

Correspondence should be addressed to Dr. Nora D Volkow, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5274, Bethesda, MD 20892. Email: nvolkow{at}nida.nih.gov

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