Early-life adversity, dopamine, and decision-making processes

早年逆境、多巴胺和决策过程

• 批准号: RGPIN-2016-04548
• 负责人: Lovic, Vedran
• 金额: $ 2.04万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=657997
• 关键词: Early; life; adversity; dopamine; decision

Individuals seek rewards essential for survival and procreation, such as food, water, shelter, and mates. Yet numerous decisions have to be made about these rewards – timing of collecting rewards, choice between different classes of rewards, as well as within category choices. These processes are exceptionally complex as they integrate homeostatic and affective states, ‘plans', as well as what has previously been learned. Through instrumental learning individuals learn how to obtain these rewards. However, other processes, such as Pavlovian conditioning can influence these processes as well. Pavlovian conditioned stimuli can alter motivational states and facilitate instrumental learning. In fact, numerous experimental studies have investigated how Pavlovian conditioning can facilitate instrumental learning and performance. However, there are many real-life situations in which Pavlovian stimuli are in conflict with goal-directed behaviour and instrumental learning. These Pavlovian-instrumental conflicts are poorly understood at the psychological and neurobiological levels. In fact, there are very few studies that have investigated these phenomena.***Brain dopamine (DA) systems, involving both midbrain DA nuclei as well as their downstream projections sites (ventral and dorsal striatum), are involved in both Pavlovian and instrumental learning. These DA systems can be altered by various experiences, especially by inconsistencies with primary rewards during development (e.g., food, parental care, social contact etc.). The overall objectives of my research program (long-term) are to understand how early-life adversities (e.g., social isolation) alter brain DA systems and how in turn these changes alter learning and decision-making processes. With this specific proposal (short term objectives), our working hypothesis is that early adversity increases the incentive value of Pavlovian cues, rendering them irresistible and having inordinate control over behaviour, and leading to deficits in instrumental learning and performance. Specifically we will have three objectives:***• To characterize how early adversity alters the attribution of incentive salience to Pavlovian cues and how these, in turn, alter performance in instrumental learning tasks***• To identify the neurobiological substrates involved in Pavlovian-instrumental conflicts***• To characterize DA neurotransmission following early adversity, in Pavlovian-instrumental conflict situations. ***Each segment of this research program contributes uniquely to the overall objective but they all share a common and novel conceptual framework. The results of this research program will shed light on the psychology and neurobiology of decision-making processes in conflicting motivational situations.**

个体寻求生存和繁殖所必需的奖励，如食物、水、住所和配偶。然而，对于这些奖励，必须做出许多决定--获取奖励的时机、不同类别的奖励之间的选择，以及类别选择。这些过程非常复杂，因为它们整合了动态平衡和情感状态、“计划”以及以前学到的东西。通过工具性学习，个人学会如何获得这些回报。然而，其他过程，如巴甫洛夫条件反射，也可以影响这些过程。巴甫洛夫条件刺激可以改变动机状态，促进工具性学习。事实上，许多实验研究已经调查了巴甫洛夫条件反射如何促进器乐学习和表现。然而，在许多现实生活中，巴甫洛夫式的刺激与目标导向的行为和工具性学习相冲突。这些巴甫洛夫式的工具冲突在心理和神经生物学层面上很少被理解。事实上，很少有研究研究这些现象。*脑多巴胺(DA)系统既涉及中脑DA核，也涉及其下游投射部位(腹侧和背侧纹状体)，参与巴甫洛夫学习和工具性学习。这些发展援助系统可能会因各种经历而改变，特别是在发育过程中与主要奖励不一致(例如，食物、父母照料、社会联系等)。我的研究计划(长期)的总体目标是了解早期生活中的逆境(例如，社会隔离)如何改变大脑DA系统，以及这些变化如何反过来改变学习和决策过程。有了这个具体的建议(短期目标)，我们的工作假设是，早期逆境增加了巴甫洛夫线索的激励价值，使它们不可抗拒，并对行为进行了过度控制，并导致工具性学习和表现方面的缺陷。具体地说，我们将有三个目标：*·表征早期逆境如何改变对巴甫洛夫线索的激励显著归因，以及这些如何反过来改变工具性学习任务中的表现*·以确定参与巴甫洛夫-工具性冲突的神经生物学底物*·表征早期逆境后巴甫洛夫-工具性冲突情境中DA神经传递的特征。*本研究计划的每个部分都对总体目标作出了独特的贡献，但它们都有一个共同的、新颖的概念框架。这一研究项目的结果将有助于揭示在相互冲突的动机情境中决策过程的心理学和神经生物学。