Genetic Deletion of Fatty Acid Amide Hydrolase Alters Emotional Behavior and Serotonergic Transmission in the Dorsal Raphe, Prefrontal Cortex, and Hippocampus
Genetic Deletion of Fatty Acid Amide Hydrolase Alters Emotional Behavior and Serotonergic Transmission in the Dorsal Raphe, Prefrontal Cortex, and Hippocampus
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DOI：
10.1038/npp.2010.80
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发表时间：
2010-09-01
影响因子：
7.6
通讯作者：
Gobbi, Gabriella
中科院分区：
文献类型：
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作者：
Bambico, Francis Rodriguez;Cassano, Tommaso;Gobbi, Gabriella
莫达非尼在化学结构、神经化学特征和行为效应方面不同于其他唤醒增强剂。迄今为止，大多数功能性神经影像学研究仅检查了莫达非尼对执行认知基础信息处理的影响，但一般而言，认知增强剂对情绪行为也有显着影响。我们研究了莫达非尼对情感处理和认知功能的神经回路的影响。本双盲安慰剂对照试验招募了健康志愿者（100 mg/天，持续7天）。他们接受了BOLD功能磁共振成像，同时执行激活杏仁核的情感信息处理任务和两个前额叶依赖的认知任务-工作记忆（WM）任务和可变注意力控制（VAC）任务。还在每个测试日进行临床评估，包括测量血压、心率、汉密尔顿焦虑量表和情绪状态（POMS）问卷。BOLD fMRI显示，与安慰剂条件相比，莫达非尼组杏仁核对恐惧刺激的反应性显着降低。在执行认知任务，WM任务和VAC任务，莫达非尼减少BOLD信号在前额叶皮层和前扣带回。虽然没有统计学意义，但莫达非尼有减少焦虑、减少疲劳惯性和增加活力活动以及减少愤怒敌意的趋势。与兴奋剂相比，低剂量的莫达非尼具有独特的生理特征：它可以提高前额叶皮质认知信息处理的效率，同时抑制杏仁核（一个与焦虑有关的大脑区域）对威胁性刺激的反应。Neuropsychopharmacology（2010）35，2101-2109; doi：10.1038/npp.2010.83; 2010年6月16日在线发表
Modafinil differs from other arousal-enhancing agents in chemical structure, neurochemical profile, and behavioral effects. Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition, but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior, too. We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions. Healthy volunteers were enrolled in this double-blinded placebo-controlled trial (100 mg/day for 7 days). They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks-a working memory (WM) task and a variable attentional control (VAC) task. A clinical assessment that included measurement of blood pressure, heart rate, the Hamilton anxiety scale, and the profile of mood state (POMS) questionnaire was also performed on each test day. BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition. During executive cognition tasks, a WM task and a VAC task, modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate. Although not statistically significant, there were trends for reduced anxiety, for decreased fatigue-inertia and increased vigor-activity, as well as decreased anger-hostility on modafinil. Modafinil in low doses has a unique physiologic profile compared with stimulant drugs: it enhances the efficiency of prefrontal cortical cognitive information processing, while dampening reactivity to threatening stimuli in the amygdala, a brain region implicated in anxiety. Neuropsychopharmacology (2010) 35, 2101-2109; doi:10.1038/npp.2010.83; published online 16 June 2010