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

药物成瘾是一种慢性复发性疾病，其特征是管理不善的动机行为。成瘾的合理和有效的药物治疗的形成需要了解奖励快感的神经生物学基础和奖励价值的表征。先前的研究已经暗示内源性阿片系统作为奖励的情感特性的一个潜在的中介。此外，内源性阿片类物质已被证明可以调节大脑奖励回路中的谷氨酸传输。有趣的是，这些基底前脑区域的谷氨酸传输与动机行为密切相关，特别是对滥用物质的行为。因此，本建议的具体目的是区分内源性阿片系统的作用，在消费性快感，奖励价值的代表性和一般的动机唤醒使用一种新的工具范式，专门设计来区分这些组件的目标导向的行动。我们还将阐明基础前脑curcuitry调节奖励快感和/或奖励值的表示内的解剖学基板，并测试内源性阿片类药物通过改变这些结构中的谷氨酸释放来调节奖励值表示的假设。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纵以及电酶促过氧化聚吡咯和谷氨酸氧化酶涂层的铂微阵列生物传感器来实现，用于实时记录突触外谷氨酸在异质性蔗糖寻找-摄取链中具有完善的适口性分析。已经确定的是，在这个链条的寻求部分上的表现反映了奖励的具体价值。因此，这些数据将阐明阿片和阿片受体对奖赏快感和价值编码的调节。这项研究的长期目标是了解阿片系统如何调节奖励价值和动机。这项工作将提供一个基础，了解如何内源性奖励过程中出错成瘾行为。内源性阿片和谷氨酸系统与几类滥用物质的强化和成瘾特性有关。我们打算了解这些系统如何调解奖励处理的具体组成部分。因此，这项研究不仅将为我们了解成瘾药物如何篡夺奖励系统提供信息，还将为潜在药物治疗研究提供信息。

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.