Haloperidol blocks dorsal striatum activity but not analgesia in a placebo paradigm
Abstract
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.
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A recent study found that the ventral striatum might not be causally involved in placebo analgesia, but rather linked to phenomena associated with placebo analgesia, such as reward processing and learning.
“This result is consistent with a recent study, in which Wrobel and colleagues (Wrobel et al., 2014) found that the ventral striatum might not be causally involved in placebo analgesia, but rather linked to phenomena associated with placebo analgesia, such as reward processing and learning.”
From Distinct neural representations of placebo and nocebo effects (2015) · cites this paper as Wrobel et al., 2014
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Spisák, T., Hartmann, H., Zunhammer, M., Kincses, B., Wiech, K., Wager, T. D., & Bingel, U. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.21.655287
Self-citation
- Authors
- Wrobel, N., Wiech, K., Forkmann, K., Ritter, C., & Bingel, U.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- John Radcliffe Hospital (GB)
- University of Duisburg-Essen (DE)
- Corresponding author
- Wrobel, Nathalie
- Venue
- Cortex
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 57
- Pages
- 60-73
- ISSN
- 0010-9452 (ISSN-L)
- OpenAlex
- W2093705132
- Cited by
- 45
- References
- 59
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 2
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIHR Oxford Biomedical Research Centre
- University of Bath
- Deutsche Forschungsgemeinschaft (BI 789/2-1)
- Bundesministerium für Bildung und Forschung (01GQ0808)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- placebo analgesia, haloperidol, dorsal striatum, dopamine D2/D3 receptors, dopamine signaling, placebo response, pain modulation, reward processing
- MeSH terms
- Adolescent, Adult, Analgesia, Brain, Brain Mapping, Female, Haloperidol, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neural Pathways, Pain, Placebos, Dopamine Antagonists, Young Adult
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