Journal
NEUROIMAGE
Volume 39, Issue 3, Pages 1266-1273Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2007.09.059
Keywords
PET imaging; raclopride; addiction; caudate; putamen; conditioned responses; D2 receptors
Funding
- NCRR NIH HHS [M01 RR010710, M01RR10710] Funding Source: Medline
- NIDA NIH HHS [R01 DA006278, DA06278-15] Funding Source: Medline
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Imaging studies have shown an association between dopamine increases in striatum and cue induced craving in cocaine abusers. However, the extent to which dopamine increases reflect a primary rather than a secondary response to the cues remains unclear. Here we evaluated the extent to which dopamine increases by themselves can induce craving in cocaine abusers. Using PET and [C-11]raclopride (D2 receptor radioligand sensitive to competition with endogenous dopamine) we show that in cocaine abusers (n=20) oral methylphenidate (20 mg), which significantly increased dopamine in striatum, did not induce craving unless subjects were concomitantly exposed to cocaine cues (video scenes of subjects self-administering cocaine). This suggests that dopamine increases associated with conditioned cues are not primary responses but reflect downstream stimulation of dopamine cells (presumably glutamatergic afferents from prefrontal cortex and/or amygdala). Inasmuch as afferent stimulation of dopamine neurons results in phasic cell firing these findings suggest that fast dopamine increases, in contrast to the slow dopamine increases as achieved when using oral methylphenidate (mimicking tonic dopamine cell firing), are required for cues to trigger craving. The fact that methylphenidate induced craving only when given with the cocaine cues highlights the context dependency of methylphenidate's effects and suggests that its use for the treatment of ADHD subjects with co-morbid drug abuse should not increase craving. Published by Elsevier Inc.
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