Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests: A model for reward pathology with effects of agomelatine
Mouse psychosocial stress reduces motivation and cognitive function in operant reward tests: A model for reward pathology with effects of agomelatine
复制标题
DOI：
10.1016/j.euroneuro.2016.06.009
复制
发表时间：
2016-09-01
影响因子：
5.6
通讯作者：
Pryce, Christopher R.
中科院分区：
文献类型：
--
作者：
Bergamini, Giorgio;Cathomas, Flurin;Pryce, Christopher R.
抑郁的一个主要领域是奖励动机的降低。翻译自动化测试可以应用于人类和动物，以研究操作型奖赏行为、潜在缺陷的病因-病理生理学，以及抗抑郁治疗的效果。进行了三个相互关联的实验，以调查慢性心理社会压力对小鼠操作行为的抑郁相关影响。(A)非操纵小鼠接受蔗糖强化的复杂逆转学习(CRL)测试；相对于赋形剂(VEH)，急性抗抑郁药agomelatine(前，25 mg/kg P.O.)更多的逆转。(B)小鼠在第1-15天接受慢性社会挫败(CSD)或对照处理(CON)，在第10-22天接受AGO或VEH。在第15天的蔗糖递增比率计划动机测试中，CSD小鼠做出的反应较少；AGO倾向于逆转这一效应。在第22天的CRL测试中，CSD小鼠完成的逆转较少；AGO倾向于增加CSD小鼠的逆转，这与适应性毅力的增加有关。(C)在家中持续接触水和糖精溶液的小鼠暴露在CSD或Con中；CSD小鼠对糖精和水的反应较少，在活动期喝的糖精较少，在非活动期喝更多的水。在另一个单独的CSD队列中，重复前一次对这些家庭笼子操作者和消耗性变化没有影响。总体而言，这项研究表明，小鼠的心理社会应激导致操作奖励测试中与抑郁相关的动机和认知能力下降；AGO部分逆转了这些缺陷，为预测有效性提供了证据。(C)2016年爱思唯尔和ECNP。版权所有。
A major domain of depression is decreased motivation for reward. Translational automated tests can be applied in humans and animals to study operant reward behaviour, aetio-pathophysiology underlying deficits therein, and effects of antidepressant treatment. Three inter-related experiments were conducted to investigate depression-relevant effects of chronic psychosocial stress on operant behaviour in mice. (A) Non-manipulated mice were trained on a complex reversal learning (CRL) test with sucrose reinforcement; relative to vehicle (VEH), acute antidepressant agomelatine (AGO, 25 mg/kg p.o.) increased reversals. (B) Mice underwent chronic social defeat (CSD) or control handling (CON) on days 1-15, and were administered AGO or VEH on days 10-22. In a progressive ratio schedule motivation test for sucrose on day 15, CSD mice made fewer responses; AGO tended to reverse this effect. In a CRL test on day 22, CSD mice completed fewer reversals; AGO tended to increase reversals in CSD mice associated with an adaptive increase in perseveration. (C) Mice with continuous operant access to water and saccharin solution in the home cage were exposed to CSD or CON; CSD mice made fewer responses for saccharin and water and drank less saccharin in the active period, and drank more water in the inactive period. In a separate CSD cohort, repeated AGO was without effect on these home cage operant and consummatory changes. Overall, this study demonstrates that psychosocial stress in mice leads to depression-relevant decreases in motivation and cognition in operant reward tests; partial reversal of these deficits by AGO provides evidence for predictive validity. (C) 2016 Elsevier B.V. and ECNP. All rights reserved.