Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues.
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 [(11)C]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.
Volkow
Nora D
ND
National Institute on Drug Abuse, Bethesda MD 20892, USA; National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA. nvolkow@nida.nih.gov
Wang
Gene-Jack
GJ
Telang
Frank
F
Fowler
Joanna S
JS
Logan
Jean
J
Childress
Anna-Rose
AR
Jayne
Millard
M
Ma
Yeming
Y
Wong
Christopher
C
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology*; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D020891:Raclopride; D011795:Surveys and Questionnaires; D014054:Tomography
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate; D020891:Raclopride; D004298:Dopamine