The Influence of Stress on Decision-Making: Effects of CRF and Dopamine Antagonism in the Nucleus Accumbens.
The Influence of Stress on Decision-Making: Effects of CRF and Dopamine Antagonism in the Nucleus Accumbens.
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DOI：
10.3389/fpsyt.2021.814218
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发表时间：
2021
影响因子：
4.7
通讯作者：
Phillips PEM
中科院分区：
文献类型：
--
作者：
Williams RG;Li KH;Phillips PEM
伏核核心的促肾上腺皮质激素释放因子(CRF)的作用包括促进多巴胺的释放和诱导应激幼稚动物的条件性位置偏爱。然而，在两天的重复强迫游泳应激(RFSS)后，这两种效应都不存在，这表明CRF和多巴胺之间存在应激敏感的相互作用。为了确定这种机制在多大程度上影响基于奖励的综合决策，我们使用了一项可操作的并发选择任务，让小鼠在两个装有蔗糖溶液的液体容器或送水的容器中进行选择。在最初的训练后，将促肾上腺皮质激素释放因子或多巴胺拮抗剂、α-螺旋促肾上腺皮质激素释放因子(9-41)和氟苯硫醇或赋形剂分别注入伏隔核核心。接下来，动物接受rFSS，被重新引入这项任务，并重新进行测试。在应激之前，小鼠表现出明显的蔗糖偏好而不是水，在整个过程中，小鼠鼻子对蔗糖容器的戳比对水容器的总戳要多。没有观察到性别差异。压力并没有强烈地影响偏好指标，但与压力天真、时间匹配的同行相比，确实增加了试验遗漏的数量。有趣的是，给药不影响蔗糖的选择，但增加了他们在试验间隔期的鼻戳偏好，增加了试验遗漏，并减少了ITI期间的总鼻戳。相比之下，微量注射α-螺旋CRF(9-41)并不影响遗漏或ITI鼻戳，但产生了与选择指标上的压力的交互作用。这些数据表明，多巴胺和CRF都与压力相互作用，影响任务中的表现，但影响不同的行为方面。
The actions of corticotropin-releasing factor (CRF) in the core of the nucleus accumbens including increasing dopamine release and inducing conditioned place preference in stress-naïve animals. However, following two-day, repeated forced swim stress (rFSS), neither of these effects are present, indicating a stress-sensitive interaction between CRF and dopamine. To ascertain the degree to which this mechanism influences integrated, reward-based decision making, we used an operant concurrent-choice task where mice could choose between two liquid receptacles containing a sucrose solution or water delivery. Following initial training, either a CRF or dopamine antagonist, α-helical CRF (9–41) and flupenthixol, respectively, or vehicle was administered intracranially to the nucleus accumbens core. Next, the animals underwent rFSS, were reintroduced to the task, and were retested. Prior to stress, mice exhibited a significant preference for sucrose over water and made more total nose pokes into the sucrose receptacle than the water receptacle throughout the session. There were no observed sex differences. Stress did not robustly affect preference metrics but did increase the number of trial omissions compared to their stress-naïve, time-matched counterparts. Interestingly, flupenthixol administration did not affect sucrose choice but increased their nosepoke preference during the inter-trial interval, increased trial omissions, and decreased the total nosepokes during the ITI. In contrast, microinjections of α-helical CRF (9–41) did not affect omissions or ITI nosepokes but produced interactions with stress on choice metrics. These data indicate that dopamine and CRF both interact with stress to impact performance in the task but influence different behavioral aspects.
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DOI：
10.1111/j.1460-9568.2009.07044.x
发表时间：
2010-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
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10.1073/pnas.1419770111
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