Funayama Takuya, Ikeda Yumiko, Tateno Amane, Takahashi Hidehiko, Okubo Yoshiro, Fukayama Haruhisa, Suzuki Hidenori
Anesthesiology and Clinical Physiology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.
Psychopharmacology (Berl). 2014 Aug;231(16):3217-28. doi: 10.1007/s00213-014-3499-0. Epub 2014 Feb 28.
The nucleus accumbens (NAc) works as a key brain structure of the reward system, in which reward-related neural activity is well correlated with dopamine release from mesolimbic dopaminergic neurons.
Since modafinil can modulate dopaminergic transmission through re-uptake inhibition of dopamine, we investigated whether modafinil affects the reward-related brain activity in the NAc in healthy subjects.
Twenty healthy participants underwent two series of functional magnetic resonance imaging while performing monetary incentive delay task in which they were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money, under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD) activation signals during gain and loss anticipations were analyzed in the NAc as an a priori region of interest as well as the whole brain.
Modafinil significantly changed subjective feelings toward positive ones. The activation of BOLD signals was observed during gain anticipation under the placebo and modafinil conditions in the left and bilateral NAc, respectively. The modafinil condition showed significantly higher BOLD signal change at the highest gain (+¥500) cue compared to the placebo condition.
The present study showed that modafinil affects reward processing in the NAc in healthy subjects through enhancing more positive anticipation, and it may provide a basis for the use of this drug for treating anhedonia observed in psychiatric disorders.
伏隔核(NAc)是奖赏系统的关键脑结构,其中与奖赏相关的神经活动与中脑边缘多巴胺能神经元释放多巴胺密切相关。
由于莫达非尼可通过抑制多巴胺再摄取来调节多巴胺能传递,我们研究了莫达非尼是否会影响健康受试者伏隔核中与奖赏相关的脑活动。
20名健康参与者在莫达非尼或安慰剂条件下进行货币激励延迟任务时,接受了两组功能磁共振成像检查。在该任务中,他们被提示预期并对快速呈现的目标做出反应,以获得或避免损失不同金额的金钱。作为先验感兴趣区域,对伏隔核以及全脑在预期获利和损失期间的血氧水平依赖(BOLD)激活信号进行了分析。
莫达非尼显著改变了对积极情绪的主观感受。在安慰剂和莫达非尼条件下,分别在左侧和双侧伏隔核的预期获利期间观察到BOLD信号激活。与安慰剂条件相比,在最高获利(+500日元)提示下,莫达非尼条件下的BOLD信号变化显著更高。
本研究表明,莫达非尼通过增强更积极的预期来影响健康受试者伏隔核中的奖赏处理,这可能为使用该药物治疗精神疾病中观察到的快感缺失提供依据。