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Impact of a high-fat fructose diet from early life to young adulthood on spatial memory deficits in male rats: Assessments using the Barnes maze and Morris water maze.

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Title: Impact of a high-fat fructose diet from early life to young adulthood on spatial memory deficits in male rats: Assessments using the Barnes maze and Morris water maze.
Authors: Izadi MS; Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, , Iran. Electronic address: minna.izadi@gmail.com., Salimi M; Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. Electronic address: mina.salimi22@yahoo.com., Eskandari F; Neurophysiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: farzaneeskandari86@yahoo.com., Zardooz H; Neurophysiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: homeira_zardooz@sbmu.ac.ir.
Source: Physiology & behavior [Physiol Behav] 2026 Oct 15; Vol. 315, pp. 115446. Date of Electronic Publication: 2026 Jul 10.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier Science Country of Publication: United States NLM ID: 0151504 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-507X (Electronic) Linking ISSN: 00319384 NLM ISO Abbreviation: Physiol Behav Subsets: MEDLINE
Imprint Name(s): Publication: New York NY : Elsevier Science
Original Publication: Oxford, Eng., Long Island City, Pergamon Press.
MeSH Terms: Fructose*/adverse effects , Fructose*/administration & dosage , Memory Disorders*/etiology , Memory Disorders*/chemically induced , Diet, High-Fat*/adverse effects , Maze Learning*/drug effects , Maze Learning*/physiology , Spatial Memory*/drug effects , Spatial Memory*/physiology, Hippocampus/metabolism ; Hippocampus/drug effects ; Interleukin-1beta/metabolism ; Oxidative Stress/drug effects ; Corticosterone/blood ; Morris Water Maze Test/drug effects ; Animals ; Male ; Rats ; Rats, Wistar ; Animals, Newborn ; Disease Models, Animal ; Age Factors
Abstract: Background: Chronic intake of a high-fat-fructose (HFF) diet may result in oxidative stress and inflammation, ultimately leading to cognitive impairments. To assess potential spatial memory deficits resulting from HFF diet consumption from birth to young adulthood and the impact of 4-phenylbutyric acid (4-PBA) treatment, two spatial memory assessment tests were utilized: the Barnes maze (BM) and the Morris water maze (MWM) tests.
Methods: After delivery, dams and their pups were randomly assigned to either the control (Ctrl) or the HFF diet group. After weaning, male pups were subdivided into the four groups based on the diet and treatment: Ctrl-DMSO, Ctrl-4-PBA, HFF-DMSO, and HFF-4-PBA. They continued their respective diets for five weeks, followed by a ten-day drug injection period. Behavioral tests, including BM and MWM tests, were performed on the sixth and seventh days of drug treatment, respectively. Finally, plasma corticosterone levels, as well as hippocampal levels of interleukin-1beta (IL-1β) and oxidative stress markers, were measured.
Results: Early life to young adulthood consumption of HFF diet caused hippocampal IL-1β and malondialdehyde (MDA) contents, alongside a decrease in glutathione (GSH) level. These alterations were accompanied by memory impairment, decreased time spent in the target area, and increased latency to first in the HFF-DMSO group. 4-PBA administration improved the adverse changes in HFF-fed rats. Based on the behavioral findings, the BM appeared to be more sensitive than the MWM in identifying spatial memory impairments.
Conclusion: Overall, a prolonged HFF diet consumption led to inflammation and oxidative stress in the hippocampus, which was associated with memory impairments in young adult male rats. The findings indicate that 4-PBA may represent a promising therapeutic approach to mitigate the negative biochemical and behavioral effects of such dietary exposure. Furthermore, the BM test is recommended as a useful tool for assessing potential spatial memory deficits in dietary intervention studies.
(Copyright © 2026 Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in this work.
Contributed Indexing: Keywords: 4-Phenylbutyric acid; Barnes maze; High-fat-fructose diet; Hippocampus inflammation and oxidative stress; Morris water maze; Spatial memory
Substance Nomenclature: 30237-26-4 (Fructose)
0 (Interleukin-1beta)
W980KJ009P (Corticosterone)
Entry Date(s): Date Created: 20260710 Date Completed: 20260807 Latest Revision: 20260807
Update Code: 20260808
DOI: 10.1016/j.physbeh.2026.115446
PMID: 42431499
Database: MEDLINE
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  Data: Impact of a high-fat fructose diet from early life to young adulthood on spatial memory deficits in male rats: Assessments using the Barnes maze and Morris water maze.
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  Data: <searchLink fieldCode="AU" term="%22Izadi+MS%22">Izadi MS</searchLink>; Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, , Iran. Electronic address: minna.izadi@gmail.com.<br /><searchLink fieldCode="AU" term="%22Salimi+M%22">Salimi M</searchLink>; Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran; Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran. Electronic address: mina.salimi22@yahoo.com.<br /><searchLink fieldCode="AU" term="%22Eskandari+F%22">Eskandari F</searchLink>; Neurophysiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: farzaneeskandari86@yahoo.com.<br /><searchLink fieldCode="AU" term="%22Zardooz+H%22">Zardooz H</searchLink>; Neurophysiology Research Center, Institute of Neuroscience and Cognition, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: homeira_zardooz@sbmu.ac.ir.
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  Data: <searchLink fieldCode="JN" term="%220151504%22">Physiology & behavior</searchLink> [Physiol Behav] 2026 Oct 15; Vol. 315, pp. 115446. <i>Date of Electronic Publication: </i>2026 Jul 10.
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  Data: <searchLink fieldCode="MM" term="%22Fructose%22">Fructose*</searchLink>/<searchLink fieldCode="MM" term="%22Fructose+adverse+effects%22">adverse effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Fructose%22">Fructose*</searchLink>/<searchLink fieldCode="MM" term="%22Fructose+administration+%26+dosage%22">administration & dosage</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory+Disorders%22">Memory Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+Disorders+etiology%22">etiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Memory+Disorders%22">Memory Disorders*</searchLink>/<searchLink fieldCode="MM" term="%22Memory+Disorders+chemically+induced%22">chemically induced</searchLink> <br /><searchLink fieldCode="MM" term="%22Diet%2C+High-Fat%22">Diet, High-Fat*</searchLink>/<searchLink fieldCode="MM" term="%22Diet%2C+High-Fat+adverse+effects%22">adverse effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Maze+Learning%22">Maze Learning*</searchLink>/<searchLink fieldCode="MM" term="%22Maze+Learning+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Maze+Learning%22">Maze Learning*</searchLink>/<searchLink fieldCode="MM" term="%22Maze+Learning+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Spatial+Memory%22">Spatial Memory*</searchLink>/<searchLink fieldCode="MM" term="%22Spatial+Memory+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Spatial+Memory%22">Spatial Memory*</searchLink>/<searchLink fieldCode="MM" term="%22Spatial+Memory+physiology%22">physiology</searchLink><br /><searchLink fieldCode="MH" term="%22Hippocampus%22">Hippocampus</searchLink>/<searchLink fieldCode="MH" term="%22Hippocampus+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Hippocampus%22">Hippocampus</searchLink>/<searchLink fieldCode="MH" term="%22Hippocampus+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Interleukin-1beta%22">Interleukin-1beta</searchLink>/<searchLink fieldCode="MH" term="%22Interleukin-1beta+metabolism%22">metabolism</searchLink> ; <searchLink fieldCode="MH" term="%22Oxidative+Stress%22">Oxidative Stress</searchLink>/<searchLink fieldCode="MH" term="%22Oxidative+Stress+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Corticosterone%22">Corticosterone</searchLink>/<searchLink fieldCode="MH" term="%22Corticosterone+blood%22">blood</searchLink> ; <searchLink fieldCode="MH" term="%22Morris+Water+Maze+Test%22">Morris Water Maze Test</searchLink>/<searchLink fieldCode="MH" term="%22Morris+Water+Maze+Test+drug+effects%22">drug effects</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%22">Rats</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%2C+Wistar%22">Rats, Wistar</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%2C+Newborn%22">Animals, Newborn</searchLink> ; <searchLink fieldCode="MH" term="%22Disease+Models%2C+Animal%22">Disease Models, Animal</searchLink> ; <searchLink fieldCode="MH" term="%22Age+Factors%22">Age Factors</searchLink>
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  Label: Abstract
  Group: Ab
  Data: Background: Chronic intake of a high-fat-fructose (HFF) diet may result in oxidative stress and inflammation, ultimately leading to cognitive impairments. To assess potential spatial memory deficits resulting from HFF diet consumption from birth to young adulthood and the impact of 4-phenylbutyric acid (4-PBA) treatment, two spatial memory assessment tests were utilized: the Barnes maze (BM) and the Morris water maze (MWM) tests.<br />Methods: After delivery, dams and their pups were randomly assigned to either the control (Ctrl) or the HFF diet group. After weaning, male pups were subdivided into the four groups based on the diet and treatment: Ctrl-DMSO, Ctrl-4-PBA, HFF-DMSO, and HFF-4-PBA. They continued their respective diets for five weeks, followed by a ten-day drug injection period. Behavioral tests, including BM and MWM tests, were performed on the sixth and seventh days of drug treatment, respectively. Finally, plasma corticosterone levels, as well as hippocampal levels of interleukin-1beta (IL-1β) and oxidative stress markers, were measured.<br />Results: Early life to young adulthood consumption of HFF diet caused hippocampal IL-1β and malondialdehyde (MDA) contents, alongside a decrease in glutathione (GSH) level. These alterations were accompanied by memory impairment, decreased time spent in the target area, and increased latency to first in the HFF-DMSO group. 4-PBA administration improved the adverse changes in HFF-fed rats. Based on the behavioral findings, the BM appeared to be more sensitive than the MWM in identifying spatial memory impairments.<br />Conclusion: Overall, a prolonged HFF diet consumption led to inflammation and oxidative stress in the hippocampus, which was associated with memory impairments in young adult male rats. The findings indicate that 4-PBA may represent a promising therapeutic approach to mitigate the negative biochemical and behavioral effects of such dietary exposure. Furthermore, the BM test is recommended as a useful tool for assessing potential spatial memory deficits in dietary intervention studies.<br /> (Copyright © 2026 Elsevier Inc. All rights reserved.)
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  Data: Declaration of competing interest The authors declare no conflicts of interest in this work.
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        Value: 10.1016/j.physbeh.2026.115446
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        Text: English
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      – SubjectFull: Hippocampus drug effects
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      – SubjectFull: Interleukin-1beta metabolism
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      – SubjectFull: Male
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      – SubjectFull: Fructose adverse effects
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      – SubjectFull: Diet, High-Fat adverse effects
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      – SubjectFull: Spatial Memory drug effects
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      – SubjectFull: Spatial Memory physiology
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      – TitleFull: Impact of a high-fat fructose diet from early life to young adulthood on spatial memory deficits in male rats: Assessments using the Barnes maze and Morris water maze.
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              Text: 2026 Oct 15
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