Cocaine blocks the reuptake of dopamine, a neurotransmitter involved i
n the control of movement, cognition, motivation and reward. This lead
s to an increase in extracellular dopamine; the reinforcing effect of
cocaine is associated with elevated dopamine levels in the nucleus acc
umbens(1,2). But addiction to cocaine involves other effects, such as
craving, loss of control and compulsive drug intake; the role of the d
opamine system in these effects is less well-understood. We therefore
used positron emission tomography (PET) to compare the responses of co
caine addicts and normal controls to intravenous methylphenidate, a dr
ug that, like cocaine, causes an increase in synaptic dopamine(3). Add
icts showed reduced dopamine release in the striatum, the brain region
where tile nucleus accumbens is located, and also had a reduced 'high
' relative to controls. In contrast, addicts showed an increased respo
nse to methylphenidate in the thalamus (a region that conveys sensory
input to the cortex). This thalamic response was associated with cocai
ne craving and was not seen in control subjects. Thus, our findings ch
allenge the notion that addiction involves an enhanced striatal dopami
ne response to cocaine and/or an enhanced induction of euphoria. Moreo
ver, they suggest a participation of thalamic dopamine pathways in coc
aine addiction, a possibility that merits further investigation.