Tsumura Kampo Research Laboratories, Tsumura & Co., Ibaraki, Japan.
Center for Advanced Kampo Medicine and Clinical Research, Juntendo Graduate School of Medicine, Tokyo, Japan.
PLoS One. 2019 Sep 3;14(9):e0222076. doi: 10.1371/journal.pone.0222076. eCollection 2019.
Depression and anxiety are common psychiatric disorders that can occur throughout an individual's lifetime. Numerous pathways underlying the onset of these diseases have been identified in rodents using a social defeat stress protocol, whereby socially defeated individuals exhibit depression- and/or anxiety-like phenotypes that typically manifest as social avoidance behavior. However, most studies in this field have been conducted using young adult mice; therefore, information about social defeat stress-related behavioral phenotypes in older mice is limited. In this study, we exposed groups of young adult (8-16 weeks old) and aged (24 months old) C57BL/6J mice to mild social defeat stress by challenging them with aggressive CD1 mice while restricting the intensity of aggression to protect the animals from severe injuries. We then identified stress-induced behavioral changes and compared their expression between the age groups and with a non-defeated (non-stressed) control group. We found that the stressed mice in both age groups exhibited similar reduced social interactions that were indicative of increased social avoidance behavior. Moreover, unlike the young stressed and control groups, only the aged stressed group showed a reduced preference for sucrose, which was correlated with social avoidance behavior. Also, the aged stressed mice exhibited an attenuated defeat-induced increase in water intake. These findings reveal that aging alters behavioral phenotypes after social defeat and that the hedonic behavior of aged mice is more vulnerable to social defeat compared with younger mice.
抑郁和焦虑是常见的精神疾病，可发生于个体的整个生命周期。使用社交挫败应激方案，在啮齿动物中已经确定了这些疾病发作的许多潜在途径，通过这种方案，被社交挫败的个体表现出类似抑郁和/或焦虑的表型，通常表现为社交回避行为。然而，该领域的大多数研究都是使用年轻成年小鼠进行的；因此，关于老年小鼠与社交挫败相关的行为表型的信息有限。在这项研究中，我们通过用攻击性 CD1 小鼠挑战年轻成年（8-16 周龄）和老年（24 月龄）C57BL/6J 小鼠，使它们经历轻度社交挫败应激，同时限制攻击的强度，以保护动物免受严重伤害。然后，我们确定了应激诱导的行为变化，并比较了它们在不同年龄组之间的表达情况，并与非挫败（未应激）对照组进行了比较。我们发现，两个年龄组的应激小鼠都表现出类似的社交互动减少，这表明它们的社交回避行为增加。此外，与年轻应激和对照组不同，只有老年应激组表现出对蔗糖的偏好降低，这与社交回避行为有关。此外，老年应激小鼠的饮水量在挫败诱导增加方面的反应减弱。这些发现表明，衰老改变了社交挫败后的行为表型，并且与年轻小鼠相比，老年小鼠的享乐行为更容易受到社交挫败的影响。
