Effects of acute treadmill running at different intensities on activities of serotonin and corticotropin-releasing factor neurons, and anxiety- and depressive-like behaviors in rats
Abstract
Accumulating evidence suggests that physical exercise can reduce and prevent the incidence of stress-related psychiatric disorders, including depression and anxiety. Activation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is implicated in antidepressant/anxiolytic properties. In addition, the incidence and symptoms of these disorders may involve dysregulation of the hypothalamic-pituitary-adrenal axis that is initiated by corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN). Thus, it is possible that physical exercise produces its antidepressant/anxiolytic effects by affecting these neuronal activities. However, the effects of acute physical exercise at different intensities on these neuronal activation and behavioral changes are still unclear. Here, we examined the activities of 5-HT neurons in the DRN and CRF neurons in the PVN during 30 min of treadmill running at different speeds (high speed, 25 m/min; low speed, 15m/min; control, only sitting on the treadmill) in male Wistar rats, using c-Fos/5-HT or CRF immunohistochemistry. We also performed the elevated plus maze test and the forced swim test to assess anxiety- and depressive-like behaviors, respectively. Acute treadmill running at low speed, but not high speed, significantly increased c-Fos expression in 5-HT neurons in the DRN compared to the control, whereas high-speed running significantly enhanced c-Fos expression in CRF neurons in the PVN compared with the control and low-speed running. Furthermore, low-speed running resulted in decreased anxiety- and depressive-like behaviors compared with high-speed running. These results suggest that acute physical exercise with mild and low stress can efficiently induce optimal neuronal activation that is involved in the antidepressant/anxiolytic effects.
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Glucocorticoids can activate TDO.
“On the other hand, glucocorticoids can activate TDO [90, 91], and there is a growing body of evidence suggesting that a hyperactive HPA axis often co-occurs with depression due to increased levels of glucocorticoid hormones, systemic inflammation and increased production of pro-inflammatory cytokines [90] all of which are released due to exercise-induced stress and increased intestinal perme”
From Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes (2016) · cites this paper as [90]
A hyperactive HPA axis often co-occurs with depression due to increased glucocorticoid hormones, systemic inflammation and increased production of pro-inflammatory cytokines.
“On the other hand, glucocorticoids can activate TDO [90, 91], and there is a growing body of evidence suggesting that a hyperactive HPA axis often co-occurs with depression due to increased levels of glucocorticoid hormones, systemic inflammation and increased production of pro-inflammatory cytokines [90] all of which are released due to exercise-induced stress and increased intestinal perme”
From Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes (2016) · cites this paper as [90]
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References 73 · Cited by 86
- Authors
- Otsuka, T., Nishii, A., Amemiya, S., Kubota, N., Nishijima, T., & Kita, I.
- Affiliations
- Tokyo Metropolitan University (JP)
- Corresponding author
- Kita, Ichiro
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 298
- Issue
- Pt B
- Pages
- 44-51
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W1910037881
- Cited by
- 86
- References
- 73
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 12 · 2023: 6 · 2022: 9 · 2021: 9 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 9
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (25350819)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- exercise intensity, serotonergic neurons, dorsal raphe nucleus, corticotropin-releasing hormone neurons, paraventricular nucleus, Fos expression, anxiety-like behavior, depression-like behavior, antidepressant effects of exercise, hypothalamic-pituitary-adrenal axis
- MeSH terms
- Acute Disease, Animals, Anxiety Disorders, Corticotropin-Releasing Hormone, Depressive Disorder, Disease Models, Animal, Exercise Therapy, Male, Motor Activity, Neurons, Paraventricular Hypothalamic Nucleus, Random Allocation, Running, Serotonin, Stress, Psychological, Proto-Oncogene Proteins c-fos, Rats, Wistar, Dorsal Raphe Nucleus
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