Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095, USA.
J Neurosci. 2011 May 18;31(20):7291-9. doi: 10.1523/JNEUROSCI.0363-11.2011.
Deviations in reward sensitivity and behavioral flexibility, particularly in the ability to change or stop behaviors in response to changing environmental contingencies, are important phenotypic dimensions of several neuropsychiatric disorders. Neuroimaging evidence suggests that variation in dopamine signaling through dopamine D(2)-like receptors may influence these phenotypes, as well as associated psychiatric conditions, but the specific neurocognitive mechanisms through which this influence is exerted are unknown. To address this question, we examined the relationship between behavioral sensitivity to reinforcement during discrimination learning and D(2)-like receptor availability in vervet monkeys. Monkeys were assessed for their ability to acquire, retain, and reverse three-choice, visual-discrimination problems, and once behavioral performance had stabilized, they received positron emission tomography (PET) scans. D(2)-like receptor availability in dorsal aspects of the striatum was not related to individual differences in the ability to acquire or retain visual discriminations but did relate to the number of trials required to reach criterion in the reversal phase of the task. D(2)-like receptor availability was also strongly correlated with behavioral sensitivity to positive, but not negative, feedback during learning. These results go beyond electrophysiological findings by demonstrating the involvement of a striatal dopaminergic marker in individual differences in feedback sensitivity and behavioral flexibility, providing insight into the neural mechanisms that are affected in neuropsychiatric disorders that feature these deficits.
奖励敏感性和行为灵活性的偏差，特别是在根据环境变化改变或停止行为的能力，是几种神经精神障碍的重要表型维度。神经影像学证据表明，多巴胺 D2 样受体的多巴胺信号传递的变异可能会影响这些表型以及相关的精神状况，但影响的具体神经认知机制尚不清楚。为了解决这个问题，我们研究了在辨别学习过程中奖励敏感性与多巴胺 D2 样受体可用性之间的关系，在恒河猴中进行了研究。评估了猴子获得、保留和反转三种选择的视觉辨别问题的能力，一旦行为表现稳定，它们就接受正电子发射断层扫描（PET）扫描。背侧纹状体中 D2 样受体的可用性与获得或保留视觉辨别能力的个体差异无关，但与任务反转阶段达到标准所需的试验次数有关。D2 样受体的可用性与学习过程中对正反馈的行为敏感性也有很强的相关性，但与负反馈无关。这些结果超越了电生理学发现，证明了纹状体多巴胺能标志物在反馈敏感性和行为灵活性的个体差异中的参与，为神经精神障碍中存在这些缺陷的神经机制提供了深入了解。
