Imaging dopamine transmission in cocaine dependence: Link between neurochemistry and response to treatment

Objective: Previous research has shown that dopamine signaling in the limbic striatum is crucial for selecting adaptive, motivated behavior and that disrupted dopamine transmission is associated with impulsive and maladaptive behavior. In humans, positron emission tomography (PET) imaging studies have shown that cocaine dependence is associated with the dysregulation of striatal dopamine signaling, which is linked to cocaine-seeking behavior. The goal of the present study was to investigate whether this association applies to the treatment setting. The authors hypothesized that dopamine signaling in the limbic striatum would be associated with response to a behavioral treatment that uses positive reinforcement to replace impulsive cocaine use with constructive personal goals. Method: Prior to treatment, cocaine-dependent subjects underwent two PET scans using [¹¹C]raclopride, before and after the administration of a stimulant (methylphenidate), for measurement of striatal dopamine D_2/3 receptor binding and presynaptic dopamine release. Results: Both of the outcome measures were lower in the volunteers who did not respond to treatment than in those who experienced a positive treatment response. Conclusions: These findings provide insight into the neurochemistry of treatment response and show that low dopamine transmission is associated with treatment failure. In addition, these data suggest that the combination of behavioral treatment with methods that increase striatal dopamine signaling might serve as a therapeutic strategy for cocaine dependence.