DECREASED STRIATAL DOPAMINERGIC RESPONSIVENESS IN DETOXIFIED COCAINE-DEPENDENT SUBJECTS

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.