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

University Of California Los Angeles, Los Angeles CA

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Abstract

[unreadable] 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. [unreadable] [unreadable] [unreadable]