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Ž. Ž . Obsessive᎐compulsive disorder OCD has been linked to abnormal function of brain serotonin 5-HT pathways. Since ondansetron is a highly selective 5-HT receptor antagonist, the present study was undertaken to investigate 3 Ž . 5-HT function in OCD. We administered m-CPP 0.08 mgrkg i.v. and the potent 5-HT antagonist, ondansetron 3 3 Ž . Ž 0.15 mgrkg i.v. , to 11 OCD patients. All of the subjects received four separate challenges m-CPP q placebo, . m-CPP q ondansetron, ondansetron q placebo and placebo q placebo . In comparison to placebo, administration of m-CPP was associated with significant behavioral effects, particularly self-rated measures of anxiety, altered self-reality, functional deficit and OCD symptoms. Pretreatment with ondansetron did not affect any of the self-rated behavioral symptoms. After administration of m-CPP relative to placebo, significant increases in plasma cortisol and prolactin were found. These changes were not affected by ondansetron. In conclusion, our results do not support the hypotheses that 5-HT receptor-mediated mechanisms modulate m-CPP's behavioral and neuroendocrine effects in 3 patients with OCD. ᮊ

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