High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions
Open accessAbstract
Several psychiatric disorders involve abnormalities of interoception and associated neural circuitry centered on the insula. The development of interventions modulating interoceptive circuits could lead to novel treatment approaches for these disorders. The 5-HT3 receptor antagonist ondansetron is a good candidate for the modulation of interoceptive circuits, as 5-HT3 receptors are located abundantly on sensory pathways and ondansetron has shown some clinical utility in disorders characterized by sensory and interoceptive abnormalities. The present study tested the ability of three different doses of ondansetron to engage neural regions involved in interoception to determine the drug's utility as a therapeutic agent to target circuit abnormalities in patients. Fifty-three healthy subjects were randomized to receive a single 8-mg (n = 18), 16-mg (n = 17), or 24-mg (n = 18) dose of ondansetron and placebo before MRI scanning on separate days. Subjects performed an fMRI task previously shown to engage interoceptive circuitry in which they viewed videos depicting body movements/sensation and control videos. The results revealed a highly significant relationship between dosage and activation in bilateral insula, somatosensory and premotor regions, cingulate cortex, and temporal cortex for control but not body-focused videos. These effects were driven by a robust reduction in activation for ondansetron compared to placebo for the 24-mg group, with weaker effects for the 16-mg and 8-mg groups. In conclusion, high-dose ondansetron reduces activation of several areas important for interoception, including insula and sensorimotor cortical regions. This study reveals the potential utility of this drug in modulating hyperactivity in these regions in patients.
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Single high doses of ondansetron reduce activation in the insula, precentral and postcentral gyri, and cingulate cortex.
“Single high doses of ondansetron, a 5-HT3 receptor antagonist FDA approved for severe nausea and vomiting [104], reduce activation in the insula, precentral and postcentral gyri, and cingulate cortex [105].”
From Toward a neurocircuit-based taxonomy to guide treatment of obsessive-compulsive disorder (2021) · cites this paper as [105]
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- Authors
- Stern, E. R., Shahab, R., Grimaldi, S. J., Leibu, E., Murrough, J. W., Fleysher, L., Parides, M. K., Coffey, B. J., Burdick, K. E., & Goodman, W. K.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- Hofstra University (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Miami (US)
- Brigham and Women's Hospital (US)
- Baylor College of Medicine (US)
- Corresponding author
- Stern, Emily R.
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2018-08-08
- Volume
- 44
- Issue
- 2
- Pages
- 390-398
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6300545
- OpenAlex
- W2885869118
- Cited by
- 27
- References
- 69
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 2 · 2018: 1
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R21MH107589)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ondansetron, 5-HT3 receptor antagonists, interoception, insula, sensorimotor cortex, somatosensory cortex, premotor cortex, cingulate cortex, temporal cortex, dose-response relationship, human motion perception, bodily sensations, mental illness, neural circuit modulation
- MeSH terms
- Adult, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Serotonin Antagonists, Ondansetron, Young Adult, Interoception
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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