Pavlovian influences on reward-seeking behavior

描述（由申请人提供）：成瘾复发的常见形式是由于暴露于以前与药物递送相关的线索或环境而引起的。药物配对条件刺激（CSs）增加激励动机或“渴望”的能力表明，药物暴露的奖励特性可能与通过巴甫洛夫激励学习过程预测药物递送的CSs相关。最近的研究提出了一种可能性，即由于反复接触药物导致的神经适应，前吸毒者中CSs强迫寻求奖励行为的能力得到增强。为了充分探索这一假设，有必要更深入地了解巴甫洛夫对寻求奖励行为的影响背后的动机过程，以及反复接触药物对这些过程的影响。本研究探讨了药物致敏对巴甫洛夫线索影响寻求奖励行为能力的影响，其总体目标是描述安非他明致敏大鼠对与奖励相关的CSs反应性增强的动机过程。本研究利用巴甫洛夫-工具转移（Pavlovian-instrumental transfer， PIT）范式来评估结果显著性和一般唤醒对工具行为选择和强度的影响。这些实验对于理解药物暴露改变奖励预测线索对奖励寻求行为的影响的过程具有重要意义，并将为进一步研究巴甫洛夫激励过程的神经系统和分子机制及其在药物滥用暴露中的调节提供基础。此外，这些研究对于设计治疗策略来治疗复发是很重要的，这是基于对巴甫洛夫对寻求奖励行为影响的相关因素的理解。公共卫生相关性：拟议的研究涉及对药物滥用障碍至关重要的行为过程，因此与公共卫生高度相关。此外，研究结果可能有助于制定治疗策略，以防止因再次暴露于药物相关线索而引起的复发。

DESCRIPTION (provided by applicant): A prevalent form of relapse in addiction is caused by exposure to cues or contexts formerly paired with drug delivery. The ability of drug-paired conditioned stimuli (CSs) to increase incentive motivation, or "craving", indicates that the rewarding properties of drug exposure can be associated with CSs predicting their delivery through a Pavlovian incentive learning process. Recent research raises the possibility that, as a consequence of neuroadaptations resulting from repeated drug exposure, the ability of CSs to compel reward-seeking behavior is enhanced among former drug users. To fully explore this hypothesis, a greater understanding is necessary of the motivational processes that underlie Pavlovian influences on reward-seeking behavior generally, as well as the effects of repeated drug exposure on these processes. This proposal examines the effect of drug sensitization on the ability of Pavlovian cues to influence reward-seeking behavior, with the overall goal of characterizing the motivational processes that underlie the enhanced responsiveness to reward-associated CSs in amphetamine-sensitized rats. The proposed experiments make use of Pavlovian-instrumental transfer (PIT) paradigm to assess the role of outcome saliency and general arousal in determining the choice and intensity of instrumental actions during PIT. These experiments are important for understanding the process through which drug exposure alters the influence of reward-predictive cues on reward-seeking behavior, and will serve as the basis for further research into the neural systems and molecular mechanisms underlying Pavlovian incentive processes and their modulation by exposure to drugs of abuse. Furthermore, these studies will be important in devising therapeutic strategies to treat relapse based on an understanding of the relevant factors that underlie Pavlovian influences on reward-seeking behavior. PUBLIC HEALTH RELEVANCE: The proposed research addresses behavioral processes that are central to substance abuse disorders, and thus is highly relevant to public health. Furthermore, the research findings may be useful in devising therapeutic strategies to prevent relapse caused by re-exposure to drug-associated cues.