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ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1572956
Early emergence of motivational and hedonic feeding deficits in the TgF344-AD rat model of Alzheimer's disease
Provisionally accepted
Sean B Ostlund1*
Grace Chen2
Alisa Kosheleff2
Lindsay M Lueptow3
Irina Zhuravka3
Sally Ann Frautschy4Hoa Lam2Nigel Maidment2*- 1Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, CA, United States
- 2Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA, United States
- 3Behavioral Testing Core, Department of Psychology, University of California at Los Angeles, Los Angeles, CA 90025, USA, Los Angeles, CA, United States
- 4Geriatric Research Education and Clinical Center, Veterans Greater Los Angeles HealthCare System, Departments of Neurology and Medicine, University of California, Los Angeles, Los Angeles, United States
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Alzheimer's disease (AD) is characterized by progressive cognitive decline and has a long prodromal phase during which subclinical cognitive deficits and neuropsychiatric symptoms may begin to emerge. Apathy, defined as a lack of motivation or volition, is increasingly recognized as a core feature and a potentially early marker of AD. Despite its significance, apathy-like behavior has been underexplored in transgenic models of AD. We performed a longitudinal analysis of apathy-like behavior using the well-established TgF344-AD rat model. We compared male and female TgF344-AD and wildtype rats on hedonic (palatable food intake) and motivational (progressive ratio) assays during early (3-4 months), intermediate (6-7 months), and later (9-10 months) stages of adulthood. We found that female TgF344-AD rats exhibited early and persistent deficits in motivational and hedonic feeding, emerging at 3-4 months and 6-7 months, respectively. During a battery of cognitive tests conducted after 12-14 months of age, TgF344-AD rats exhibited reduced exploratory behavior, which may also be indicative of an apathy-like loss of investigatory drive. Our findings highlight the TgF344-AD rat as a valuable model for studying early apathy-like behavior in AD and underscore the need to consider sex differences in AD research to better understand the prodromal phase of this disease.
Keywords: Alzheimer's, Apathy, Anhedonia, Dementia, avolition
Received: 07 Feb 2025; Accepted: 08 Apr 2025.
Copyright: © 2025 Ostlund, Chen, Kosheleff, Lueptow, Zhuravka, Frautschy, Lam and Maidment. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Sean B Ostlund, Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, 92697, CA, United States
Nigel Maidment, Hatos Center for Neuropharmacology, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, CA, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.