Acute intravenous administration of ondansetron and m-CPP, alone and in combination, in patients with obsessive-compulsive disorder (OCD): behavioral and biological results

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Obsessive-compulsive disorder (OCD) is associated with dysregulated brain serotonin (5-HT) pathways.
• Selective serotonin reuptake inhibitors (SSRIs) are primary OCD treatments, suggesting a role for serotonin.
• The specific involvement of 5-HT3 receptors in OCD pathophysiology remains unclear.

Purpose of the Study:

• To investigate the role of serotonin 5-HT3 receptor function in patients with obsessive-compulsive disorder.
• To determine if ondansetron, a selective 5-HT3 receptor antagonist, modulates the effects of m-CPP in OCD.

Main Methods:

• Eleven patients diagnosed with OCD underwent a double-blind, placebo-controlled study.
• Participants received intravenous challenges of m-CPP (a serotonin agonist) and ondansetron (a 5-HT3 antagonist) or placebos in a counterbalanced order.
• Behavioral symptoms, anxiety, self-reality, functional deficit, OCD symptoms, plasma cortisol, and prolactin levels were measured.

Main Results:

• Administration of m-CPP significantly increased self-rated anxiety, altered self-reality, functional deficit, and OCD symptoms compared to placebo.
• Ondansetron pretreatment did not significantly alter any of the m-CPP-induced behavioral or neuroendocrine responses.
• Increases in plasma cortisol and prolactin following m-CPP were not affected by ondansetron.

Conclusions:

• The findings do not support the hypothesis that 5-HT3 receptor-mediated mechanisms play a significant role in modulating the behavioral and neuroendocrine effects of m-CPP in individuals with OCD.
• This suggests that 5-HT3 receptor antagonism may not be a viable therapeutic strategy for OCD.
• Further research is needed to fully elucidate the complex role of serotonin pathways in OCD.