5HT3 antagonism abolishes the emotion potentiated startle effect in humans

Rationale: The serotonergic system has been implicated in emotional processing in animals and humans. Although the contribution of different receptor subtypes has been hypothesised, there have been few direct tests of this in human subjects. Objectives: The current study aimed to explore the involvement of the serotonin type 3 (5HT(3)) receptor subtype in a battery of emotional processing tasks previously found to be sensitive to SSRI administration. Materials and methods: Healthy volunteers were randomised to receive the 5HT(3) antagonist, ondansetron (12 mg, oral), or placebo in a double blind between groups design. Emotional processing was assessed using three tasks: affective modulation of the startle reflex, emotional categorisation and memory and facial expression recognition. Subjective state ratings, blood pressure and pulse were also collected before and after ondansetron and placebo. Results: Ondansetron was well tolerated and did not affect subjective measures of mood, anxiety or well-being in these healthy volunteers. However, the emotion potentiated effect was abolished in the volunteers receiving ondansetron. Facial expression recognition and emotional memory were not significantly affected. Conclusions: These results suggest an involvement of 5HT(3) receptors in certain aspects of fear processing in humans. These effects are consistent with anxiolytic actions of 5HT(3) antagonism in animal models and suggest that the 5HT(3) receptor may play a role in the effects of serotonergic manipulations on fear and anxiety.