Involvement of the Nucleus Accumbens in Chocolate-induced Cataplexy

Involvement of the Nucleus Accumbens in Chocolate-induced Cataplexy
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DOI:
10.1038/s41598-020-61823-4
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发表时间:
2020-03-18
期刊:
影响因子:
4.6
通讯作者:
Kuwaki, Tomoyuki
Kuwaki, Tomoyuki
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Su, Jingyang;Li, Zhi;Kuwaki, Tomoyuki

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快乐是身心健康的关键。为了进一步了解所涉及的大脑机制,我们利用发作性睡动物模型中发生的猝厥作为定量行为测量,因为它是由与快乐相关的行为触发的,例如人类的笑声和小鼠的美味食物。在这里,我们报道了在食欲素神经元切除的小鼠中,在巧克力诱导的猝倒开始时,伏隔核(NAc)外壳的吻侧部分被强烈激活。我们用伊博滕酸在NAc局部损伤,观察动物的行为。卒中发作次数与病变大小呈负相关。我们还通过测量舌头对蜂蜜的反应来检测对美味食物的享乐反应,这也被发现与病变大小呈负相关。接下来,我们使用氯氮平n -氧化物通过病毒DREADD表达激活或灭活NAc。正如预期的那样,中风发作次数随着激活而增加,随着失活而减少,而生理盐水对照注射没有变化。DREADD实验中的享乐反应各不相同,在小鼠中表现为增加和减少。这些结果表明,NAc的吻侧部分在触发猝倒和享乐性面部运动中起着至关重要的作用。由于NAc也与动机行为有关,我们认为NAc是涉及幸福的关键大脑结构之一,是积极情绪相关行为的驱动力。
Happiness is key for both mental and physical well-being. To further understand the brain mechanisms involved, we utilized the cataplexy that occurs in narcoleptic animal models as a quantitative behavioral measure because it is triggered by actions associated with happiness, such as laughter in humans and palatable foods in mice. Here we report that the rostral part of the nucleus accumbens (NAc) shell is strongly activated during the beginning of chocolate-induced cataplexy in orexin neuron-ablated mice. We made a local lesion in the NAc using ibotenic acid and observed the animals' behavior. The number of cataplexy bouts was negatively correlated to the lesion size. We also examined the hedonic response to palatable food by measuring the number of tongue protrusions in response to presentation of honey, which was also found to be negatively correlated to the lesion size. Next, we used clozapine N-oxide to either activate or inactivate the NAc through viral DREADD expression. As expected, the number of cataplexy bouts increased with activation and decreased with inactivation, and saline control injections showed no changes. Hedonic response in the DREADD experiment varied and showed both increases and decreases across mice. These results demonstrated that the rostral part of the NAc plays a crucial role in triggering cataplexy and hedonic orofacial movements. Since the NAc is also implicated in motivated behavior, we propose that the NAc is one of the key brain structures involved in happiness and is a driving force for positive emotion-related behaviors.