Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, China.
Sci Rep. 2020 Mar 18;10(1):4958. doi: 10.1038/s41598-020-61823-4.
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.
幸福是身心健康的关键。为了进一步了解涉及的大脑机制，我们利用发作性睡病动物模型中发生的猝倒作为一种定量行为测量方法，因为它是由与幸福相关的行为触发的，例如人类的笑声和老鼠的美味食物。在这里，我们报告在食欲素神经元缺失的小鼠巧克力诱导猝倒开始时，伏隔核壳的喙部被强烈激活。我们使用异硫氰酸酯在 NAc 中进行局部损伤，并观察动物的行为。猝倒发作的次数与损伤大小呈负相关。我们还通过测量对蜂蜜呈现时的舌头伸出次数来检查对美味食物的享乐反应，发现这也与损伤大小呈负相关。接下来，我们使用氯氮平 N-氧化物通过病毒 DREADD 表达来激活或失活 NAc。正如预期的那样，随着激活，猝倒发作的次数增加，随着失活，猝倒发作的次数减少，而盐水对照注射没有变化。在 DREADD 实验中，享乐反应因小鼠而异，既有增加也有减少。这些结果表明，NAc 的喙部在触发猝倒和享乐性口面部运动方面起着关键作用。由于 NAc 也与动机行为有关，我们提出 NAc 是参与幸福感的关键大脑结构之一，是与积极情绪相关行为的驱动力。
