Timing of exercise differentially modulates fear memory and hippocampal neurotransmitters in male rats
Persistent URL
Author(s)
Bennett, Samuel
Blair, R. Shelby
Allegheny College
Avadhanula, Kaushik
Birkett, Mitchell H.
Palapa, Citlali
Maren, Stephen
Nagaya, Naomi
Sato, Shogo
Date Issued
May 1, 2026
Abstract
Exercise promotes neurogenesis and enhances memory consolidation while reducing the retention of aversive memories and anxiety-like behaviors. While our previous work found that acute exercise alters neurotransmitter concentrations, including dopamine and serotonin, in a time-of-day-dependent manner, the long-term effects of chronically timed exercise on neurotransmitter dynamics and behavioral phenotypes remain unclear. To examine whether the daily timing of a chronic exercise intervention modulates its impact on neurotransmitter profiles and fear responses, male rats were conditioned using a Pavlovian contextual fear approach, then assigned to a 4-week treadmill exercise intervention performed during the early (ZT14) or late (ZT22) active phase or a time-matched sham-exercise control group. One day after completing training, rats underwent a context retrieval test in the middle of active phase (ZT18), and hippocampal neurotransmitters were quantified using UPLC–MRM/MS. Rats subjected to sham-exercise at ZT22 exhibited higher freezing than sham-exercised rats at ZT14, whereas exercise interventions at ZT22 selectively attenuated freezing. Histamine, acetylcholine, and GABA exhibited significant exercise × time interactions. Direct neurotransmitter–freezing correlations were weak after false discovery rate control, consistent with a network-level reorganization rather than a single transmitter driver. These findings suggest that vulnerability to aversive memory expression can be buffered by exercise, if timed appropriately, and that exercise reshapes hippocampal neuromodulatory tone in a circadian–phase–dependent manner, supporting the potential of exercise timing as a chronotherapeutic strategy to enhance stress resilience and mental wellbeing.
Journal
Frontiers in Neuroscience
Citation
Bennett S, Blair RS, Avadhanula K, Birkett MH, Palapa C, Maren S, Nagaya N and Sato S (2026) Timing of exercise differentially modulates fear memory and hippocampal neurotransmitters in male rats. Front. Neurosci. 20:1824029. doi: 10.3389/fnins.2026.1824029
Publisher
Frontiers Media SA
Version of Article
Enhanced Version of Record
DOI
10.3389/fnins.2026.1824029
ISSN
1662-453X
Rights
© 2026 Bennett, Blair, Avadhanula, Birkett, Palapa, Maren, Nagaya and Sato. 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) and the copyright owner(s) 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.
Type of Publication
Journal Article
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