Opioid and Glutamate Modulation of Reward Value During Goal-Directed Behavior

描述（由申请人提供）：药物成瘾是一种慢性，复发性障碍，其特征是缺乏管理的动机行为。要形成合理有效的药物治疗成瘾，就必须理解奖励享乐症的神经生物学基础和奖励价值的表征。先前的研究暗示了内源性阿片系统作为奖励情感特性的潜在中介。此外，内源性阿片类药物已被证明可以调节大脑奖赏回路中的谷氨酸传递。有趣的是，这些基底前脑区域的谷氨酸传递与动机行为密切相关，特别是对滥用物质的行为。因此，本研究的具体目的是利用一种新的工具范式来区分内源性阿片系统在完成性享乐、奖励价值表征和一般动机唤醒中的作用，该范式是专门为区分目标导向行为的这些组成部分而设计的。我们还将阐明基底前脑回路中调节奖励快感/和/或奖励价值表征的解剖学基础，并验证内源性阿片类物质通过这些结构中谷氨酸释放的变化来调节奖励价值表征的假设。这些目标将通过使用内源性LI阿片受体系统的中枢和外周操作，以及电酶氧化多吡罗和谷氨酸氧化酶包被的铂微阵列生物传感器来实现，用于在异质蔗糖寻找-摄取链中实时记录突触外谷氨酸，并进行完善的可食性分析。已经确定的是，在这个链条的寻找部分的表现反映了奖励的特定价值。因此，这些数据将阐明阿片和谷氨酸能对奖励快感和价值编码的调节。这项研究计划的长期目标是了解阿片系统如何调节奖励价值和动机。这项工作将为理解成瘾行为中内源性奖励过程如何出错提供基础。内源性阿片和谷氨酸系统与几种滥用物质的强化和成瘾特性有关。我们打算了解这些系统是如何调节奖励处理的特定组成部分的。因此，这项研究不仅可以让我们了解奖励系统是如何被成瘾药物篡夺的，还可以研究潜在的药物治疗方法。

DESCRIPTION (provided by applicant): Drug addiction is a chronic, relapsing disorder characterized by poorly managed motivated behavior. The formation of rational and effective pharmacotherapies for addictions necessitates an understanding of the neurobiological underpinnings of reward hedonia and the representation of reward value. Previous research has implicated the endogenous opioid systems as a potential mediator of the affective properties of reward. Moreover, endogenous opioids have been shown to modulate glutamate transmission in the brain reward circuitry. Interestingly, glutamate transmission in these basal forebrain regions is highly implicated in motivated behavior, particularly towards abused substances. Therefore the specific aims of this proposal are to differentiate the role of the endogenous opioid systems in consummatory hedonia, reward value representation and general motivational arousal using a novel instrumental paradigm designed specifically to distinguish these components of goal-directed actions. We will also elucidate the anatomical substrates within basal forebrain curcuitry regulating reward hedonia/and or the representation of reward value, and test the hypothesis that endogenous opioids modulate reward value representation through changes in glutamate release in these structures. These aims will be accomplished by using central and peripheral manipulation of the endogenous LI opioid receptor system as well as electroenzymatic overoxidized polypyrrole and glutamate oxidase-coated platinum micro-array biosensors for real-time recordings of extrasynaptic glutamate during a heterogeneous sucrose seeking-taking chain with a consummatory palatibility analyssi. It has been established that performance on the seeking component of this chain reflects the reward's specific value. Therefore, these data will elucidate the opioid and glutamatergic modulation ofreward hedonia and the encoding of value. It is the long-term objective of this research proposal to gain an understanding of how the opioid system regulates reward value and motivation. This work will provide a basis for comprehending how the endogenous reward processes go awry during addictive behavior. The endogenous opioid and glutamate systems are implicated in the reinforcing and addictive properties of several classes of abused substances. We intend to understand how these systems mediate specific components of reward processing. Consequently, this research will inform not only our understanding of how the reward systems may be usurped by addictive drugs, but also research on potential pharmacotherapies.