The decision to engage in an action leading to a rewarding outcome is governed by several factors that may vary with age. Primary among these is the value placed on the reward at the time of the decision, which is continually updated on the basis of previous emotional experience with the reward. Cues associated with reward experience also impact decision-making through a Pavlovian incentive motivation process. Endogenous opioids play a major role in mediating emotional responsiveness to palatable food rewards through actions in the nucleus accumbens/ventral pallidum, and independently facilitate instrumental incentive learning via mu opioid receptors in the basolateral amygdala. Dopamine transmission in the nucleus accumbens is essential for the invigorating effects of reward-associated cues. The goal of this proposal is to examine whether developmental transitions in endogenous opioid and dopamine transmission in these brain regions manifest as shifts in the manner in which adolescent, middle-aged, and aged rodents react to changes in experienced reward value and to environmental cues predictive of reward. We will use licking architecture during consumption of sweet solutions to assess how emotional experience of reward (palatability) changes over the lifespan and an instrumental incentive learning task to parse the effects of aging on how the emotional impact of a reward is translated into a goal value used in the decision-making process. The Pavlovian-to- instrumental transfer test will assess the ability of reward-paired cues to initiate and invigorate reward-seeking actions and how this process changes over the lifespan. The role of developmental shifts in opioid and dopamine transmission in the shifting influence of these factors across ages will be determined using central pharmacological manipulations, viral-mediated gene transfer, in vivo measures of enkephalin and dopamine release, and mice with targeted conditional manipulation of pro-enkephalin expression. Understanding how aging impacts cue-evoked incentive motivation, reward palatability, and incentive learning may inform development of targeted cognitive-behavioral and pharmacological therapies for age-dependent decision- making impairments and behavioral control disorders.

Public Health Relevance

This project will study the impact of emotional experience and environmental cues on decision-making across the lifespan and will examine the neurochemical underpinnings of such shifts in behavior. The results of this study have important implications for treating impaired decision-making in the young and elderly.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG045380-02
Application #
8898698
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Gerald, Melissa S
Project Start
2014-08-01
Project End
2019-05-31
Budget Start
2015-06-15
Budget End
2016-05-31
Support Year
2
Fiscal Year
2015
Total Cost
$379,646
Indirect Cost
$128,986
Name
University of California Los Angeles
Department
Type
Organized Research Units
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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