High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions

Emily R. Stern, Rebbia Shahab, Stephanie J. Grimaldi, Evan Leibu, James W. Murrough, Lazar Fleysher, Michael K. Parides, Barbara J. Coffey, Katherine E. Burdick, Wayne K. Goodman

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalNeuropsychopharmacology
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Ondansetron
Brain
Receptors, Serotonin, 5-HT3
Kinesthesis
Sensation Disorders
Placebos
Serotonin 5-HT3 Receptor Antagonists
Aptitude
Gyrus Cinguli
Temporal Lobe
Pharmaceutical Preparations
Psychiatry
Healthy Volunteers
Magnetic Resonance Imaging
Therapeutics
Interoception

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Stern, E. R., Shahab, R., Grimaldi, S. J., Leibu, E., Murrough, J. W., Fleysher, L., ... Goodman, W. K. (Accepted/In press). High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions. Neuropsychopharmacology. https://doi.org/10.1038/s41386-018-0174-x

High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions. / Stern, Emily R.; Shahab, Rebbia; Grimaldi, Stephanie J.; Leibu, Evan; Murrough, James W.; Fleysher, Lazar; Parides, Michael K.; Coffey, Barbara J.; Burdick, Katherine E.; Goodman, Wayne K.

In: Neuropsychopharmacology, 01.01.2018.

Research output: Contribution to journalArticle

Stern, ER, Shahab, R, Grimaldi, SJ, Leibu, E, Murrough, JW, Fleysher, L, Parides, MK, Coffey, BJ, Burdick, KE & Goodman, WK 2018, 'High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions', Neuropsychopharmacology. https://doi.org/10.1038/s41386-018-0174-x
Stern, Emily R. ; Shahab, Rebbia ; Grimaldi, Stephanie J. ; Leibu, Evan ; Murrough, James W. ; Fleysher, Lazar ; Parides, Michael K. ; Coffey, Barbara J. ; Burdick, Katherine E. ; Goodman, Wayne K. / High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions. In: Neuropsychopharmacology. 2018.
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