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.