Haloperidol blocks dorsal striatum activity but not analgesia in a placebo paradigm

Although placebo analgesia has been associated with an engagement of the endogenous opioid system there is growing evidence from neuropharmacological studies for an involvement of additional neurotransmitter systems. An increased dopaminergic neurotransmission in the ventral basal ganglia that has been found during placebo analgesia suggests a role for the dopaminergic system (Scott et al., 2007). It is, however, unclear whether striatal dopaminergic activity is causally involved in this type of analgesia. This study aimed at exploring the functional role of the dopaminergic system in placebo analgesia. To this end, we investigated the effect of the dopamine D2/D3 receptor antagonist haloperidol on behavioral and neural measures of placebo analgesia using functional magnetic resonance imaging (fMRI) in healthy volunteers. We found that 2 mg haloperidol p.o. significantly reduced the correlation between dorsal striatum activity and the individual placebo response, but had no significant effect on placebo analgesia at the behavioral or neural level, as indexed by activity in sensory or pain-modulatory brain regions. Our study therefore suggests that dopaminergic neurotransmission might not be causally involved in placebo analgesia but is related to phenomena associated with placebo analgesia such as reward processing and learning.