Elucidating the interaction between stress- and reward-mechanisms mediating individual differences in cue motivated behaviors

阐明压力机制和奖励机制之间的相互作用，调节提示动机行为中的个体差异

• 批准号: 9916225
• 负责人: Sofia A Lopez
• 金额: $ 3.8万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9916225
• 关键词: Affect; Animal Model; Automobile Driving; Behavior; Behavioral; Biological; Brain; Clustered Regularly Interspaced Short Palindromic Repeats; Complement; Conditioned Reflex; Corticosterone; Cues; Desire for food; Disease; Dopamine; Endocrine; Environment; Exhibits; Exposure to; Faculty; Female; Food; Fostering; Foundations; Future; Genetic; Goals; Growth; Impulsivity; Incentives; Individual; Individual Differences; Investigation; Knock-out; Knowledge; Lead; Learning; Literature; Location; Manuscripts; Measures; Mediating; Mediator of activation protein; Microdialysis; Modeling; Motivation; Neurobiology; Nucleus Accumbens; Outcome; Peripheral; Pharmaceutical Preparations; Pharmacology; Phase; Phenotype; Positioning Attribute; Post-Traumatic Stress Disorders; Predictive Value; Procedures; Process; Psychopathology; Publications; Quail; Radioimmunoassay; Rattus; Relapse; Research; Rewards; Role; Sampling; Stimulus; Stress; Synaptic plasticity; System; Technical Expertise; Techniques; Training; Trauma; Work; addiction; anxiety-like behavior; behavioral response; biological adaptation to stress; classical conditioning; corticosterone receptor; drug seeking behavior; experience; incentive salience; individual variation; learning strategy; male; motivated behavior; neurobiological mechanism; neurochemistry; neuromechanism; neuropsychiatric disorder; novel; resilience; response; success; tenure track; transmission process

ABSTRACT Through associative learning processes, cues in the environment become predictors of biologically relevant stimuli (e.g. food). However, when attributed with incentive value, such cues can become powerful motivators of maladaptive behavior. For example, addicts often relapse upon exposure to cues (e.g. people, paraphernalia) previously associated with the drug-taking experience. Using an animal model that captures individual variation in the propensity to attribute incentive value to reward cues, we can investigate the neurobiological mechanisms underlying cue-motivated psychopathologies like addiction. Rats that undergo Pavlovian training, consisting of cue presentation followed by delivery of a food reward, will often develop either a sign- or goal-tracking conditioned response. For both sign-trackers (ST) and goal-trackers (GT) the cue attains predictive value, but for ST the cue also attains incentive value. The attribution of incentive value to the cue transforms it into a “motivational magnet”, rendering it attractive and desirable for ST, but not GT. It has been shown that different brain circuits are engaged in response to the cue in ST vs. GT, and that dopamine (DA) is necessary for incentive (i.e. sign-tracking), but not predictive (i.e. goal-tracking) learning processes. However, to date, little has been investigated beyond the traditional “motive” circuit in ST and GT. To expand our knowledge in this regard, I will study the interaction between stress- and reward-systems in ST and GT rats. DA has long been known to interact with corticosterone (CORT), a primary mediator of the stress-response, and in turn potentiate motivated behaviors. Given that cue-elicited DA and CORT profiles differ between ST and GT, the overarching hypothesis of my work is that DA- and CORT-integrative circuits mediate individual differences in the attribution of incentive value to reward cues. The goal of the proposed work is to identify an intersection between stress- and reward- systems that drives distinct behavioral responses to environmental stimuli. To do so, I will combine and become proficient with endocrine, neurochemical, pharmacological, genetic, and behavioral approaches and analyses. This work will elucidate potential mechanisms that may render individuals more susceptible to cue-driven psychopathologies, and provide comprehensive training towards my independent scientific growth.

摘要 通过联想学习过程，环境中的线索成为生物相关性的预测因子。 刺激（例如食物）。然而，当被赋予激励价值时，这些线索可以成为强大的激励因素， 适应不良的行为例如，成瘾者经常在暴露于线索（例如人，用具）后复发。 以前与吸毒经历有关。使用捕捉个体差异的动物模型 在将激励价值归因于奖励线索的倾向中，我们可以研究神经生物学机制， 潜在的线索驱动的精神病理学比如成瘾接受巴甫洛夫训练的大鼠，包括 提示呈现后，提供食物奖励，通常会发展出一种标志跟踪或目标跟踪 条件反应对于符号追踪者（ST）和目标追踪者（GT），线索都具有预测价值，但 对于ST，球杆也达到激励价值。将激励价值归因于线索， “动机磁铁”，使其具有吸引力和可取的ST，但不是GT。 在ST与GT中，大脑回路参与对提示的反应，多巴胺（DA）是激励所必需的 (i.e.符号跟踪），但不是预测（即目标跟踪）学习过程。然而，迄今为止， 超越传统的“动机”电路在ST和GT的调查。为了扩大我们在这方面的知识，我将 研究ST和GT大鼠应激和奖赏系统之间的相互作用。DA长期以来一直与 皮质酮（CORT），压力反应的主要介质，反过来又增强动机 行为。鉴于线索诱发的DA和CORT曲线在ST和GT之间不同， DA和CORT整合回路介导了激励归因的个体差异 奖励线索的价值。这项工作的目标是确定压力和奖励之间的交叉点， 驱动对环境刺激的不同行为反应的系统。为此，我将联合收割机 精通内分泌、神经化学、药理学、遗传学和行为学方法和分析。 这项工作将阐明潜在的机制，可能使个人更容易受到线索驱动 精神病理学，并为我的独立科学成长提供全面的培训。