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

摘要 通过联想学习过程，环境中的线索成为与生物相关的预测因子 刺激物(如食物)。然而，当被归因于激励价值时，这样的暗示可以成为强大的激励因素 适应不良的行为。例如，吸毒者经常在接触到线索(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，我们可以研究其神经生物学机制 潜在的线索驱使的心理变态，比如上瘾。接受巴甫洛夫训练的大鼠，包括 在提供食物奖励之后的线索展示，通常会形成一种手势跟踪或目标跟踪 条件性反应。对于手势跟踪器(ST)和目标跟踪器(GT)，线索都具有预测性价值，但是 对于ST来说，这条线索也具有激励价值。对球杆的激励价值的归属将其转化为 “励志磁铁”，使它具有吸引力和可取的ST，但不是GT。已经证明，不同的 大脑回路对ST和GT中的提示做出反应，而多巴胺(DA)是激励所必需的 (例如，手势跟踪)，但不是预测性(即，目标跟踪)学习过程。然而，到目前为止，几乎没有 在ST和GT的传统“动机”巡回调查之外。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。长期以来，DA一直被认为是相互作用的 皮质酮(CORT)，应激反应的主要媒介，进而增强动力 行为。鉴于线索诱发的DA和CORT曲线在ST和GT之间不同，总体假设 我的工作之一是，DA和CORT整合回路在激励归因的个体差异中起中介作用 奖励线索的价值。这项拟议工作的目标是找出压力和回报之间的交叉点 驱动对环境刺激做出不同行为反应的系统。为了做到这一点，我将结合并成为 精通内分泌、神经化学、药理学、遗传学和行为学方法和分析。 这项工作将阐明可能使个体更容易受到暗示驱动的潜在机制 精神病理学，并为我的独立科学成长提供全面的培训。

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.