Chronic non-discriminatory social defeat stress reduces effort-related motivated behaviors in male and female mice.
Chronic non-discriminatory social defeat stress reduces effort-related motivated behaviors in male and female mice.
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DOI：
10.1038/s41398-021-01250-9
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发表时间：
2021-02-15
影响因子：
6.8
通讯作者：
Samuels BA
中科院分区：
文献类型：
--
作者：
Dieterich A;Liu T;Samuels BA
奖励和动机缺陷是许多情绪障碍的突出症状，包括抑郁症。类似的奖励和努力相关的选择行为任务可以用来研究啮齿动物和人类的动机。慢性应激可诱发人类的情绪障碍和雄性啮齿类动物的适应不良奖励和动机行为。然而，尽管抑郁症在女性中更为普遍，但关于慢性压力是否会导致雌性啮齿动物在与努力相关的动机性任务中的适应不良行为以及是否存在任何行为性别差异，人们知之甚少。慢性非歧视性社会失败应激（CNSDS）是慢性社会失败应激的一种变体，对雄性和雌性小鼠都有效。我们假设，CNSDS将减少与努力相关的动机和奖励行为，包括降低对贬值结果的敏感性，减少累进比率的断点，以及改变与努力相关的选择行为。将成年雄性和雌性C57 BL/6 J小鼠的单独队列分为对照组或CNSDS组，暴露于10天的CNSDS范式，然后进行工具性奖励或努力相关行为的训练和测试。CNSDS降低动机杠杆按累进比率和转移的努力相关的选择行为从一个高回报，更容易实现低回报的男女。CNSDS在结果贬值方面造成了更微妙的损害。两者合计，CNSDS诱导适应不良的转变，努力相关的选择，并减少有动机的杠杆按下在两种性别。
Reward and motivation deficits are prominent symptoms in many mood disorders, including depression. Similar reward and effort-related choice behavioral tasks can be used to study aspects of motivation in both rodents and humans. Chronic stress can precipitate mood disorders in humans and maladaptive reward and motivation behaviors in male rodents. However, while depression is more prevalent in women, there is relatively little known about whether chronic stress elicits maladaptive behaviors in female rodents in effort-related motivated tasks and whether there are any behavioral sex differences. Chronic nondiscriminatory social defeat stress (CNSDS) is a variation of chronic social defeat stress that is effective in both male and female mice. We hypothesized that CNSDS would reduce effort-related motivated and reward behaviors, including reducing sensitivity to a devalued outcome, reducing breakpoint in progressive ratio, and shifting effort-related choice behavior. Separate cohorts of adult male and female C57BL/6 J mice were divided into Control or CNSDS groups, exposed to the 10-day CNSDS paradigm, and then trained and tested in instrumental reward or effort-related behaviors. CNSDS reduced motivation to lever press in progressive ratio and shifted effort-related choice behavior from a high reward to a more easily attainable low reward in both sexes. CNSDS caused more nuanced impairments in outcome devaluation. Taken together, CNSDS induces maladaptive shifts in effort-related choice and reduces motivated lever pressing in both sexes.
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