Anesthesiology and Clinical Physiology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Int J Neuropsychopharmacol. 2013 Aug;16(7):1461-71. doi: 10.1017/S1461145712001678. Epub 2013 Feb 13.
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.
奖励处理的主要大脑结构主要位于中脑多巴胺系统中。伏隔核（NAc）接收来自腹侧被盖区的多巴胺能投射，并作为奖励的积极激励价值的关键大脑区域。由于神经激肽-1（NK₁）受体，是 P 物质（SP）的同源受体，在 NAc 中高度表达，我们假设 SP/NK₁ 受体系统可能在人类 NAc 中的正奖励处理中发挥作用。因此，我们进行了一项功能磁共振成像（fMRI）研究，通过金钱奖励延迟任务评估 NK₁ 受体拮抗剂对人类奖励处理的影响，该任务已知会在 NAc 中引起强烈激活，特别是在获得预期期间。18 名健康成年人参加了两项 fMRI 研究系列，分别服用安慰剂或 NK₁ 受体拮抗剂 aprepitant。行为测量显示，在安慰剂和 aprepitant 治疗之间，激励线索的反应时间、命中率或自我报告的努力没有显著差异。fMRI 显示，与安慰剂治疗相比，在获得预期期间，使用 aprepitant 治疗时 NAc 中的血氧水平依赖信号明显下降。这些结果表明，SP/NK₁ 受体系统参与积极激励预期的处理，并在与奖励回路中的主要多巴胺途径相关联的情况下，在强调积极效价方面发挥作用。
