The placebo response as a reward mechanism

Placebo responses occur in a wide range of medical conditions, yet the underlying mechanisms remain poorly understood. On the basis of our observations of patients in Parkinson's disease, we have argued that the placebo effect is partly mediated by the activation of reward circuitry and that mesocorticolimbic dopamine release, particularly in the ventral striatum, plays a central role. Expectation has been shown to be critically involved in placebo responses. We argue that in patients with Parkinson's disease, placebo-induced expectation of clinical improvement is a form of expectation of reward, which results in striatal dopamine release. Reward circuitry also may be involved in other placebo responses, such as placebo analgesia, given the interactions between dopamine and endogenous opioid systems. Despite the heterogeneity of placebo responses, we propose that activation of reward circuitry may represent a common mechanism underlying the placebo effect, and that dopamine and prefrontal cortical circuits interact to produce a condition-specific physiological response.