# Identifying motivational decision making deficits underlying the apathy domain in a rat model of Alzheimers disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $194,276

## Abstract

Summary
 Apathy, defined as “lack of motivation” or a “quantitative reduction in goal-directed behavior” is a major
and prevalent (up to 72%) debilitating symptom of Alzheimer's disease and related dementias. It is also
associated with poor outcome, and is the primary cause of caregiver distress. Remarkably, however, very few
studies have probed for disrupted reward processing and goal-directed decision-making underlying the apathy
domain using rodent models of Alzheimer's disease. Apathy may result from dysfunction of one or more of the
behavioral processes necessary to achieve goal-directed behavior, including internal and external
determinants that motivate behavior, selection of goals, elaboration of a plan of action, initiation, execution,
evaluation of goals achieved and feedback control of the behavioral response.
 We will employ a battery of behavioral tasks, used routinely in our labs to probe reward and decision
making deficits in rats related to normal aging and addiction, to examine such processes in a double-
transgenic rat model of Alzheimer's disease (TgF344-AD). This model expresses a single `Swedish mutation'
human amyloid precursor protein (APPsw) gene plus a delta exon 9 mutant human presenilin-1 (PS1deltaE9)
gene and manifests age-dependent cerebral amyloidosis, including an abundance of soluble amyloid-beta, that
precedes tauopathy, gliosis, apoptopic loss of neurons in the cortex and hippocampus, and cognitive deficits.
 We will perform in-depth microstructural analysis of licking behavior during reward consumption as a
measure of experienced hedonia; instrumental incentive learning to determine how experienced reward value
is used to guide reward-seeking actions; Pavlovian-to-instrumental transfer to evaluate the motivational impact
of reward-paired cues; and progressive ratio instrumental testing as a catch-all motivational assay of
willingness to work for rewards, to test the hypothesis that these core emotional and motivational processes
are disrupted in the TgF344-AD rat. In addition to probing for an apathy phenotype at a late stage of
development when neuropathology is profound (18 months), we will also probe prior to presentation of overt
neuropathology (3 months) and at an early stage of progression (6 months), to test the hypothesis that such
deficits precede cognitive impairments in this model and that individual variability in motivation at early stages
predicts severity of cognitive deficits and neuropathology assessed later in the animals' life.
 Apathy is a core behavioral symptom of Alzheimer's disease. Identifying the neurobehavioral basis for
apathy in an animal model of the disease will provide targets for behavioral and pharmacological therapeutic
intervention. Further, demonstration that emotional and/or motivational deficits precede and predict cognitive
decline and overt neuropathology in an animal model will inform the development of tools for using measures
of apathy (and their neural correlates) as ...

## Key facts

- **NIH application ID:** 9856396
- **Project number:** 5R21AG060752-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Nigel T Maidment
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,276
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856396

## Citation

> US National Institutes of Health, RePORTER application 9856396, Identifying motivational decision making deficits underlying the apathy domain in a rat model of Alzheimers disease (5R21AG060752-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856396. Licensed CC0.

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