Short-term NK1 receptor antagonism and emotional processing in healthy volunteers

Abstract

Despite early promise in phase II, the performance of the NK1 receptor antagonist aprepitant in subsequent clinical trials has been disappointing. Healthy volunteer models of emotional processing offer a potential means by which novel drugs can be screened prior to clinical trials. Here, we consider the effect of 7 days of treatment with aprepitant in such a model. Healthy volunteers (n = 32) were randomised to receive 7-day treatment with aprepitant (125 mg) or placebo. On the seventh day, participants completed a battery of tasks measuring emotional processing previously demonstrated to be sensitive to conventional antidepressant drugs. The tasks included facial expression recognition, emotional categorisation and memory, attentional dot-probe and emotion potentiated startle task. Aprepitant abolished the emotionally potentiated startle effect and increased recognition memory for emotionally positive versus negative stimuli. In addition, the drug decreased attention to negative relative to positive emotional stimuli on the masked version of the dot-probe task. These effects were seen in the absence of any change in subjective mood. There were no effects on emotional categorisation, recall or on facial expression recognition. These results suggest that NK1 receptor antagonism does affect some aspects of emotional processing and, in particular, that it has anxiolytic-like effects. The profile of effects reported here is, however, more limited than that found in response to conventional antidepressant treatment, and this may explain disappointing results at clinical trial. Healthy volunteer models of emotional processing may be useful in closing the gap between preclinical and clinical trials.