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多巴胺D2受体拮抗后基于努力的决策和消费行为的破坏。

Disruptions in effort-based decision-making and consummatory behavior following antagonism of the dopamine D2 receptor.

作者信息

Robles Cindee F, Johnson Alexander W

机构信息

Department of Psychology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, United States.

Department of Psychology and Neuroscience Program, Michigan State University, East Lansing, MI 48824, United States.

出版信息

Behav Brain Res. 2017 Mar 1;320:431-439. doi: 10.1016/j.bbr.2016.10.043. Epub 2016 Oct 27.

DOI:10.1016/j.bbr.2016.10.043
PMID:27984049
Abstract

Dopamine is known to influence motivational processes, however the precise role of this neurotransmitter remains a contentious issue. In the current study we sought to further characterize dopamine signaling in reward-based decision-making and consummatory behavior in mice, via lateral ventricle infusion of the dopamine D2 receptor antagonist eticlopride. In Experiment 1, we examined effort-based decision-making, in which mice had a choice between one lever, where a single response led to the delivery of a low value reward (2% sucrose); and a second lever, which led to a higher value reward (20% sucrose) that gradually required more effort to obtain. As the response schedule for the high value reward became more strict, low dose (4μg in 0.5μl) central infusions of eticlopride biased preference away from the high value reward, and toward the lever that led to the low value reward. Similarly, a higher dose of eticlopride (8μg in 0.5μl) also disrupted choice responding for the high value reward, however it did so by increasing omissions. In Experiment 2, we assessed the effects of eticlopride on consumption of 20% sucrose. The antagonist led to a dose-dependent reduction in intake, and through an analysis of licking microstructure, it was revealed that this in part reflected a reduction in the motivation to engage in consummatory behavior, rather than alterations in the evaluation of the reward. These results suggest that disruptions in D2 receptor signaling reduce the willingness to engage in effortful operant responding and consumption of a desirable outcome.

摘要

多巴胺已知会影响动机过程,然而这种神经递质的确切作用仍是一个有争议的问题。在当前的研究中,我们试图通过向侧脑室注射多巴胺D2受体拮抗剂依托必利,进一步表征小鼠基于奖励的决策和满足行为中的多巴胺信号传导。在实验1中,我们研究了基于努力的决策,即小鼠可以在一个杠杆和另一个杠杆之间进行选择,按下一个杠杆单次反应可获得低价值奖励(2%蔗糖);按下另一个杠杆则可获得高价值奖励(20%蔗糖),但逐渐需要更多努力才能获得。随着高价值奖励的反应时间表变得更加严格,低剂量(0.5微升中含4微克)的依托必利中央注射使偏好从高价值奖励偏向导致低价值奖励的杠杆。同样,较高剂量的依托必利(0.5微升中含8微克)也扰乱了对高价值奖励的选择反应,不过它是通过增加遗漏来做到这一点的。在实验2中,我们评估了依托必利对20%蔗糖消耗的影响。拮抗剂导致摄入量呈剂量依赖性减少,并且通过对舔舐微观结构的分析发现,这部分反映了参与满足行为的动机降低,而不是奖励评估的改变。这些结果表明,D2受体信号传导的破坏会降低参与有努力要求的操作性反应和消费理想结果的意愿。

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