Early life stress in male mice blunts responsiveness in a translationally-relevant reward task.
Early life stress in male mice blunts responsiveness in a translationally-relevant reward task.
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DOI：
10.1038/s41386-023-01610-7
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发表时间：
2023-11
影响因子：
7.6
通讯作者：
Carlezon Jr, William A. A.
中科院分区：
文献类型：
--
作者：
Hisey, Erin E.;Fritsch, Emma L.;Newman, Emily L.;Ressler, Kerry J.;Kangas, Brian D.;Carlezon Jr, William A. A.
早期生活压力（ELS）会在大脑中留下信号，这些信号会在整个生命周期中持续存在，并增加患精神疾病的风险，包括情绪和焦虑症。在人类中，无数形式的ELS-包括童年虐待，欺凌，贫困和创伤-越来越普遍。了解ELS的症状，包括与精神疾病相关的症状，将有助于改善治疗和预防。在这里，我们开发了一种新的程序来模拟小鼠中的人类ELS，并识别情绪和焦虑症的预防相关生物标志物。我们将雄性小鼠（C57 BL/6 J）暴露于早期（青少年）慢性社会失败压力（jCSDS），并研究了成年期的社会互动和对奖励的反应。正如预期的那样，暴露于jCSDS的小鼠在旷场社交互动测试中表现出社交回避表型。然而，蔗糖偏好测试未能证明ELS诱导的选择减少的甜味剂的解决方案，这表明没有影响奖励功能。为了探索其他任务是否对动机的变化更敏感，我们在概率奖励任务（PRT）中测试了小鼠，这是一种经常用于人类研究与抑郁症相关的奖励学习缺陷的程序。在一个触摸屏PRT变体中，该变体被反向翻译以最大限度地与人类受试者中使用的版本对齐，暴露于jCSDS的小鼠显示出对更丰富的奖励刺激产生反应偏差的趋势显着降低，这是在人类中观察到的快感缺失的标志性标志。我们的研究结果表明，跨物种利用相同端点的翻译相关程序可能有助于开发改进的模型系统，从而更准确地预测人类的结果。
Early-life stress (ELS) leaves signatures upon the brain that persist throughout the lifespan and increase the risk of psychiatric illnesses including mood and anxiety disorders. In humans, myriad forms of ELS—including childhood abuse, bullying, poverty, and trauma—are increasingly prevalent. Understanding the signs of ELS, including those associated with psychiatric illness, will enable improved treatment and prevention. Here, we developed a novel procedure to model human ELS in mice and identify translationally-relevant biomarkers of mood and anxiety disorders. We exposed male mice (C57BL/6 J) to an early-life (juvenile) chronic social defeat stress (jCSDS) and examined social interaction and responsivity to reward during adulthood. As expected, jCSDS-exposed mice showed a socially avoidant phenotype in open-field social interaction tests. However, sucrose preference tests failed to demonstrate ELS-induced reductions in choice for the sweetened solution, suggesting no effect on reward function. To explore whether other tasks might be more sensitive to changes in motivation, we tested the mice in the Probabilistic Reward Task (PRT), a procedure often used in humans to study reward learning deficits associated with depressive illness. In a touchscreen PRT variant that was reverse-translated to maximize alignment with the version used in human subjects, mice exposed to jCSDS displayed significant reductions in the tendency to develop response biases for the more richly-rewarded stimulus, a hallmark sign of anhedonia when observed in humans. Our findings suggest that translationally-relevant procedures that utilize the same endpoints across species may enable the development of improved model systems that more accurately predict outcomes in humans.
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DOI：
10.1093/ijnp/pyy038
发表时间：
2018-09-01
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Hasegawa S;Miyake Y;Yoshimi A;Mouri A;Hida H;Yamada K;Ozaki N;Nabeshima T;Noda Y
通讯作者：
Noda Y
影响因子：
14.8
作者：
Carlezon, William A., Jr.;Chartoff, Elena H.
通讯作者：
Chartoff, Elena H.
影响因子：
10.6
作者：
McCullough KM;Missig G;Robble MA;Foilb AR;Wells AM;Hartmann J;Anderson KJ;Neve RL;Nestler EJ;Ressler KJ;Carlezon WA Jr
通讯作者：
Carlezon WA Jr
DOI：
10.1038/s41386-021-01250-9
发表时间：
2022-03
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Kangas BD;Short AK;Luc OT;Stern HS;Baram TZ;Pizzagalli DA
通讯作者：
Pizzagalli DA
影响因子：
3.6
作者：
KUDRYAVTSEVA, NN;BAKSHTANOVSKAYA, IV;KORYAKINA, LA
通讯作者：
KORYAKINA, LA