Acute NK₁ receptor antagonist administration affects reward incentive anticipation processing in healthy volunteers

The primary brain structures of reward processing are mainly situated in the mid-brain dopamine system. The nucleus accumbens (NAc) receives dopaminergic projections from the ventral tegmental area and works as a key brain region for the positive incentive value of rewards. Because neurokinin-1 (NK₁) receptor, the cognate receptor for substance P (SP), is highly expressed in the NAc, we hypothesized that the SP/NK₁ receptor system might play a role in positive reward processing in the NAc in humans. Therefore, we conducted a functional MRI (fMRI) study to assess the effects of an NK₁ receptor antagonist on human reward processing through a monetary incentive delay task that is known to elicit robust activation in the NAc especially during gain anticipation. Eighteen healthy adults participated in two series of an fMRI study, taking either a placebo or the NK₁ receptor antagonist aprepitant. Behavioural measurements revealed that there was no significant difference in reaction time, hit rate, or self-reported effort for incentive cues between the placebo and aprepitant treatments. fMRI showed significant decrease in blood oxygenation-level-dependent signals in the NAc during gain anticipation with the aprepitant treatment compared to the placebo treatment. These results suggest that SP/NK₁ receptor system is involved in processing of positive incentive anticipation and plays a role in accentuating positive valence in association with the primary dopaminergic pathways in the reward circuit.