RT Journal Article
SR Electronic
T1 Cocaine Cues and Dopamine in Dorsal Striatum: Mechanism of Craving in Cocaine Addiction
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6583
OP 6588
DO 10.1523/JNEUROSCI.1544-06.2006
VO 26
IS 24
A1 Nora D. Volkow
A1 Gene-Jack Wang
A1 Frank Telang
A1 Joanna S. Fowler
A1 Jean Logan
A1 Anna-Rose Childress
A1 Millard Jayne
A1 Yeming Ma
A1 Christopher Wong
YR 2006
UL http://www.jneurosci.org/content/26/24/6583.abstract
AB 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.