Stolyarova Alexandra, O'Dell Steve J, Marshall John F, Izquierdo Alicia
University of California, Los Angeles, CA 90095, USA.
University of California, Irvine, CA 92617, USA.
Behav Brain Res. 2014 Sep 1;271:195-202. doi: 10.1016/j.bbr.2014.06.031. Epub 2014 Jun 21.
Learning from mistakes and prospectively adjusting behavior in response to reward feedback is an important facet of performance monitoring. Dopamine (DA) pathways play an important role in feedback learning and a growing literature has also emerged on the importance of serotonin (5HT) in reward learning, particularly during punishment or reward omission (negative feedback). Cognitive impairments resulting from psychostimulant exposure may arise from altered patterns in feedback learning, which in turn may be modulated by DA and 5HT transmission. We analyzed long-term, off-drug changes in learning from positive and negative feedback and associated striatal DA transporter (DAT) and frontocortical 5HT transporter (SERT) binding in rats pretreated with methamphetamine (mAMPH). Specifically, we assessed the reversal phase of pairwise visual discrimination learning in rats receiving single dose- (mAMPHsingle) vs. escalating-dose exposure (mAMPHescal). Using fine-grained trial-by-trial analyses, we found increased sensitivity to and reliance on positive feedback in mAMPH-pretreated animals, with the mAMPHsingle group showing more pronounced use of this type of feedback. In contrast, overall negative feedback sensitivity was not altered following any mAMPH treatment. In addition to validating the enduring effects of mAMPH on early reversal learning, we found more consecutive error commissions before the first correct response in mAMPH-pretreated rats. This behavioral rigidity was negatively correlated with subregional frontocortical SERT whereas positive feedback sensitivity negatively correlated with striatal DAT binding. These results provide new evidence for the overlapping, yet dissociable roles of DA and 5HT systems in overcoming perseveration and in learning new reward rules.
从错误中学习并根据奖励反馈前瞻性地调整行为是绩效监测的一个重要方面。多巴胺（DA）通路在反馈学习中起着重要作用，并且关于血清素（5HT）在奖励学习中的重要性也出现了越来越多的文献，特别是在惩罚或奖励缺失（负面反馈）期间。精神兴奋剂暴露导致的认知障碍可能源于反馈学习模式的改变，而这反过来可能由DA和5HT传递调节。我们分析了用甲基苯丙胺（mAMPH）预处理的大鼠从正性和负性反馈中学习的长期停药后变化以及相关的纹状体DA转运体（DAT）和前额叶皮质5HT转运体（SERT）结合情况。具体而言，我们评估了接受单剂量（mAMPHsingle）与递增剂量暴露（mAMPHescal）的大鼠在成对视觉辨别学习中的反转阶段。通过细粒度的逐试验分析，我们发现mAMPH预处理的动物对正性反馈的敏感性和依赖性增加，mAMPHsingle组对这种类型反馈的使用更为明显。相比之下，任何mAMPH处理后总体负性反馈敏感性均未改变。除了验证mAMPH对早期反转学习的持久影响外，我们还发现mAMPH预处理的大鼠在首次正确反应之前有更多连续的错误行为。这种行为僵化与前额叶皮质亚区域SERT呈负相关，而正性反馈敏感性与纹状体DAT结合呈负相关。这些结果为DA和5HT系统在克服固着和学习新的奖励规则中的重叠但可分离的作用提供了新证据。
