Objectives:~The overall objective of this study is to examine the effects of single doses of 8 mg, 16 mg, and 24 mg ondansetron as compared to placebo on neural mechanisms of cognition and perception in healthy individuals.~Background:~Many psychiatric disorders are associated with altered sensory experiences arising from within the body. Examples include increased experience of sensations or urges in muscles, skins, joints or visceral organs in tic disorders, OCD patients with symptoms of not just right experiences or disgust sensitivity, and impulse control disorders (ICDs) such as trichotillomania or skin-picking. In OCD, sensory phenomena occur in approximately half of patients, are associated with earlier age of onset, and may be harder to treat with classic cognitive-behavioral approaches to OCD. Of interest, sensory phenomena in OCD are associated with Tourette's syndrome and respond to pharmacological treatments primarily used for tics. As such, abnormal sensory processing may be a basic mechanism that links various psychiatric disorders.~The process of attending to body sensations is referred to as interoception, and broadly includes the detection of, or attention to, experiences arising from the viscera and soma. Research has revealed a cortical interoceptive circuit involving insula, anterior cingulate cortex (ACC), and somatomotor cortex.~Ondansetron (OND) is a good candidate for the modulation of the above-described interoceptive circuit. It is a selective 5-HT3 (serotonin) receptor antagonist that acts on both peripheral and central receptors. OND has long been used to treat nausea and vomiting due to chemotherapy, radiation therapy, anesthesia, and opioid-induced emesis. It has also been used alone or as adjunctive therapy for the treatment of both OCD and Tourette's disorder, showing some efficacy in small clinical trials. The mechanisms by which ondansetron improves symptoms in OCD and tic disorders are unknown, but a recent study found that OND application directly into the insula decreased disgust reactions in rats. This data suggests that ondansetron's clinical efficacy could be related to effects on interoceptive circuit activity in the insula and sensorimotor regions, a possibility that is being explored in the current protocol. Typical dosages for anti-emetic action is 8-24 mg. The investigator's pilot data found that a single 16 mg dose of ondansetron reduced activation of insula and somatosensory cortex in both healthy controls and patients with OCD. As a follow-up to this pilot work, the current protocol will compare the effects of three different dosages of ondansetron (8 mg, 16 mg, and 24 mg) on activation in insula and somatosensory cortex during tasks of cognition and perception in healthy adults.
This project investigates the effects of a single dose of ondansetron on brain function in healthy adults. The investigators hypothesize that there will be a dose-dependent reduction in activation of the insula and somatosensory brain regions associated with the use of ondansetron.