Exercise-associated changes in the corticosterone response to acute restraint stress: Evidence for increased adrenal sensitivity and reduced corticosterone response duration
Open accessAbstract
Exercise promotes stress resistance and is associated with reduced anxiety and reduced depression in both humans and in animal models. Despite the fact that dysfunction within the hypothalamic pituitary adrenal (HPA) axis is strongly linked to both anxiety and depressive disorders, the evidence is mixed as to how exercise alters the function of the HPA axis. Here we demonstrate that 4 weeks of voluntary wheel running was anxiolytic in C57BL/6J mice and resulted in a shorter time to peak corticosterone (CORT) and a more rapid decay of CORT following restraint stress. Wheel running was also associated with increased adrenal size and elevated CORT following systemic administration of adrenocorticotropic hormone. Finally, the HPA-axis response to peripheral or intracerebroventricular administration of dexamethasone did not suggest that wheel running increases HPA-axis negative feedback through GR-mediated mechanisms. Together these findings suggest that exercise may promote stress resilience in part by insuring a more rapid and shortened HPA response to a stressor thus affecting overall exposure to the potentially negative effects of more sustained HPA-axis activation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Stress-induced alterations may result from elevated glucocorticoid levels and differences in glucocorticoid release or sensitivity between susceptible and resilient mice.
“Such stress-induced alterations may result from elevated glucocorticoid levels and potential differences in glucocorticoid release or differences in sensitivity to glucocorticoids between susceptible and resilient mice (55).”
From Neuroanatomic differences associated with stress susceptibility and resilience (2016) · cites this paper as [55]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Stress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621 · see citing works
Endocrinology of the stress response
Charmandari, E., Tsigos, C., & Chrousos, G. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.67.040403.120816 · Cited by 1,799 · see citing works
Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis
Herman, J. P., Ostrander, M. M., Mueller, N. K., & Figueiredo, H. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.08.006 · Cited by 1,322 · see citing works
Lawlor, D. A., & Hopker, S. W. (2001) · BMJ · doi:10.1136/bmj.322.7289.763 · Cited by 995 · cited 1× · see citing works
“In humans, exercise is associated with a reduced incidence of stress-related psychopathology (De Moor et al, 2006; Dunn et al, 2001; Herring et al, 2010; Lawlor and Hopker, 2001), and in rodents, voluntary wheel running is associated with reduced anxiety- and depression-like behaviors (Binder et al, 2004; Fox et al, 2…”
BackgroundPhysical activity dose-response effects on outcomes of depression and anxiety
DUNN, A. L., TRIVEDI, M. H., & O???NEAL, H. A. (2001) · Medicine and Science in Sports and Exercise · doi:10.1097/00005768-200106001-00027 · Cited by 816 · see citing works
Stress, hypercortisolism and corticosteroid receptors in depression: implicatons for therapy
Holsboer, F. (2001) · Journal of Affective Disorders · doi:10.1016/s0165-0327(00)00352-9 · Cited by 575 · see citing works
Regular exercise, anxiety, depression and personality: a population-based study
De Moor, M. H. M., Beem, A. L., Stubbe, J. H., Boomsma, D. I., & De Geus, E. J. C. (2006) · Preventive Medicine · doi:10.1016/j.ypmed.2005.12.002 · Cited by 493 · see citing works
Stress and Plasticity in the Limbic System
Sapolsky, R. M. (2003) · Neurochemical Research · doi:10.1023/a:1026021307833 · Cited by 489 · see citing works
Yehuda, R., McFarlane, A. C., & Shalev, A. Y. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00276-5 · Cited by 478 · see citing works
Social isolation delays the positive effects of running on adult neurogenesis
Stranahan, A. M., Khalil, D., & Gould, E. (2006) · Nature Neuroscience · doi:10.1038/nn1668 · Cited by 467 · see citing works
The Effect of Exercise Training on Anxiety Symptoms Among Patients: A Systematic Review
Herring, M. P. (2010) · Archives of Internal Medicine · doi:10.1001/archinternmed.2009.530 · Cited by 446 · see citing works
Greenwood, B. N., Foley, T. E., Day, H. E. W., Campisi, J., Hammack, S. E., Campeau, S., Maier, S. F., & Fleshner, M. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-07-02889.2003 · Cited by 367 · see citing works
Self-citationEffects of long-term voluntary exercise on the mouse hypothalamic–pituitary–adrenocortical axis
Droste, S. K., Gesing, A., Ulbricht, S., Müller, M. B., Linthorst, A. C. E., & Reul, J. M. H. M. (2003) · Endocrinology · doi:10.1210/en.2003-0097 · Cited by 324 · see citing works
Adlard, P. A., & Cotman, C. W. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.12.039 · Cited by 265 · see citing works
Cole, M. A., Kim, P. J., Kalman, B. A., & Spencer, R. L. (2000) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(99)00045-1 · Cited by 217 · see citing works
Reber, S. O., Birkeneder, L., Veenema, A. H., Obermeier, F., Falk, W., Straub, R. H., & Neumann, I. (2006) · Endocrinology · doi:10.1210/en.2006-0983 · Cited by 212 · see citing works
Regular voluntary exercise reduces anxiety-related behaviour and impulsiveness in mice
Binder, E., Droste, S. K., Ohl, F., & Reul, J. M. H. M. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.04.017 · Cited by 188 · see citing works
Behavioral and physiological characterization of male mice under chronic psychosocial stress
Bartolomucci, A., Pederzani, T., Sacerdote, P., Panerai, A. E., Parmigiani, S., & Palanza, P. (2003) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2003.08.003 · Cited by 177 · see citing works
Plasma corticosterone response to acute and chronic voluntary exercise in female house mice
Girard, I., & Garland, T. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00465.2001 · Cited by 176 · see citing works
Droste, S. K., Chandramohan, Y., Hill, L. E., Linthorst, A. C. E., & Reul, J. M. H. M. (2007) · Neuroendocrinology · doi:10.1159/000104770 · Cited by 157 · see citing works
Role of Corticotropin-Releasing Factor (CRF) Receptors in the Anorexic Syndrome Induced by CRF
Pelleymounter, M. A., Joppa, M. A., Carmouché, M., Cullen, M. J., Brown, B. T., Murphy, B., Grigoriadis, D. E., Ling, N., & Foster, A. C. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39300-0 · Cited by 151 · see citing works
Cloning and Functional Characterization of a Family of Receptors for the Melanotropic Peptides
Cone, R. D., Mountjoy, K. G., Robbins, L. S., Nadeau, J. H., Johnson, K. R., Roselli-Rehfuss, L., & Mortrud, M. T. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb19694.x · Cited by 151 · see citing works
Fediuc, S., Campbell, J. E., & Riddell, M. C. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01416.2005 · Cited by 148 · see citing works
The consequences of uncontrollable stress are sensitive to duration of prior wheel running
Greenwood, B. N., Foley, T. E., Burhans, D., Maier, S. F., & Fleshner, M. (2005) · Brain Research · doi:10.1016/j.brainres.2004.11.037 · Cited by 141 · see citing works
Voluntary exercise in C57 mice is anxiolytic across several measures of anxiety
Salam, J., FOX, J., DETROY, E., GUIGNON, M., Wohl, D. A., & Falls, W. A. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.07.036 · Cited by 139 · see citing works
Self-citationHPA axis dysregulation in mice overexpressing corticotropin releasing hormone
Groenink, L., Dirks, A., Verdouw, P. M., Schipholt, M. L., Veening, J. G., van der Gugten, J., & Olivier, B. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01334-3 · Cited by 126 · see citing works
Risbrough, V. B., Hauger, R. L., Roberts, A. L., Vale, W., & Geyer, M. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5760-03.2004 · Cited by 123 · see citing works
Uschold‐Schmidt, N., Nyuyki, K. D., Füchsl, A. M., Neumann, I. D., & Reber, S. O. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.02.015 · Cited by 92 · see citing works
Sasse, S. K., Greenwood, B. N., Masini, C. V., Nyhuis, T. J., Fleshner, M., Day, H. E. W., & Campeau, S. (2008) · Stress · doi:10.1080/10253890801887453 · Cited by 85 · see citing works
apoE isoforms and measures of anxiety in probable AD patients and Apoe−/− mice
Robertson, J., Curley, J., Kaye, J. A., Quinn, J. F., Pfankuch, T., & Raber, J. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.06.003 · Cited by 81 · see citing works
Réus, G. Z., Abelaira, H. M., Stringari, R. B., Fries, G. R., Kapczinski, F. P., & Quevedo, J. (2012) · Metabolic Brain Disease · doi:10.1007/s11011-012-9281-2 · Cited by 80 · see citing works
Karanth, S., Linthorst, A. C. E., Stalla, G. K., Barden, N., Holsboer, F., & Reul, J. M. H. M. (1997) · Endocrinology · doi:10.1210/endo.138.8.5331 · Cited by 79 · see citing works
Campeau, S., Nyhuis, T. J., Sasse, S. K., Kryskow, E. M., Herlihy, L. E., Masini, C. V., Babb, J. A., Greenwood, B. N., Fleshner, M., & Day, H. E. W. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02007.x · Cited by 78 · see citing works
Dijkstra, I., Binnekade, R., & Tilders, F. J. H. (1996) · Endocrinology · doi:10.1210/endo.137.2.8593800 · Cited by 75 · see citing works
Droste, S. K., Schweizer, M. C., Ulbricht, S., & Reul, J. M. H. M. (2006) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01489.x · Cited by 66 · see citing works
Social subordination impairs hypothalamic–pituitary–adrenal function in female rhesus monkeys
Michopoulos, V., Reding, K. M., Wilson, M. E., & Toufexis, D. J. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.07.014 · Cited by 64 · see citing works
Self-citationSciolino, N. R., Dishman, R. K., & Holmes, P. V. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.05.001 · Cited by 60 · see citing works
Campbell, J. E., Rakhshani, N., Fediuc, S., Bruni, S. G., & Riddell, M. C. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91128.2008 · Cited by 60 · see citing works
Atrophic Cardiac Remodeling Induced by Taurine Deficiency in Wistar Rats
Pansani, M. C., Azevedo, P. S., Rafacho, B. P. M., Minicucci, M. F., Chiuso‐Minicucci, F., Zorzella-Pezavento, S. F. G., Marchini, J. S., Padovan, G. J., Fernandes, A. A. H., Matsubara, B. B., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041439 · Cited by 57 · see citing works
Bhatia, N., Jaggi, A. S., Singh, N., Anand, P., & Dhawan, R. K. (2011) · Journal of Natural Medicines · doi:10.1007/s11418-011-0535-9 · Cited by 57 · see citing works
Exercise is associated with reduction in the anxiogenic effect of mCPP on acoustic startle.
Fox, J. H., Hammack, S. E., & Falls, W. A. (2008) · Behavioral Neuroscience · doi:10.1037/0735-7044.122.4.943 · Cited by 53 · see citing works
Self-citationBroocks, A. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00056-6 · Cited by 51 · see citing works
Otsuka, T., Goto, M., Kawai, M., Togo, Y., Sato, K., Katoh, K., Furuse, M., & Yasuo, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039090 · Cited by 49 · see citing works
Broocks, A., Meyer, T., Gleiter, C. H., Hillmer-Vogel, U., George, A., Bartmann, U., & Bandelow, B. (2001) · Psychopharmacology · doi:10.1007/s002130100706 · Cited by 46 · see citing works
Buck, H. M., Hueston, C. M., Bishop, C., & Terrence Deak, B. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2388-z · Cited by 41 · see citing works
Kour, K., & Bani, S. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.001 · Cited by 39 · see citing works
Nyhuis, T. J., Masini, C. V., Sasse, S. K., Day, H. E. W., & Campeau, S. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.038 · Cited by 30 · see citing works
Han, E., Evans, T. R., & Nelson, J. F. (1998) · Journal of Nutrition · doi:10.1093/jn/128.9.1415 · Cited by 28 · see citing works
Salivary Cortisol and PTSD Symptoms in Persian Gulf War Combatants
Kellner, M. B., Baker, D. G., & Yehuda, R. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb48300.x · Cited by 19 · see citing works
Prior stress interferes with the anxiolytic effect of exercise in c57bl/6j mice.
Hare, B. D., D’Onfro, K. C., Hammack, S. E., & Falls, W. A. (2012) · Behavioral Neuroscience · doi:10.1037/a0030617 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Malhi, G. S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P. B., Fritz, K., Hopwood, M., Lyndon, B., Mulder, R., Murray, G., et al. (2015) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867415617657 · Cited by 842 · see citing works
“…using lithium as a neuroprotective agent (Soeiro-de-Souza et al., 2012), psychologically e.g., teaching cognitive reappraisal skills (Troy et al., 2010), socially e.g., improving social support (Pietrzak et al., 2009), and through lifestyle change e.g., building exercise habits (Hare et al., 2014).”
BackgroundNeuroanatomic differences associated with stress susceptibility and resilience
Anacker, C., Scholz, J., O’Donnell, K. J., Allemang-Grand, R., Diorio, J., Bagot, R. C., Nestler, E. J., Hen, R., Lerch, J. P., & Meaney, M. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.08.009 · Cited by 167 · see citing works
Maier, S. F. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.09.003 · Cited by 143 · see citing works
Zhang, T., & Kong, J. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1567603 · Cited by 19 · see citing works
- Authors
- Hare, B. D., Beierle, J. A., Toufexis, D. J., Hammack, S. E., & Falls, W. A.
- Affiliations
- University of Vermont (US)
- Corresponding author
- Falls, William A
- Venue
- Neuropsychopharmacology
- Published
- 2013-11-26
- Volume
- 39
- Issue
- 5
- Pages
- 1262-1269
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3957122
- OpenAlex
- W2022014186
- Cited by
- 85
- References
- 50
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 6 · 2016: 10 · 2015: 9 · 2014: 2
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p30gm103498-05, 8 P30 GM103498)
- National Institute of General Medical Sciences (8 P30 GM 103498, P30-GM103498)
- National Center for Research Resources (RR032135, P30RR032135)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- physical activity, wheel running, corticosterone, restraint stress, hypothalamic-pituitary-adrenal axis, stress resilience, adrenal sensitivity, anxiolytic effects, ACTH, dexamethasone, glucocorticoid receptor, negative feedback, anxiety, depression
- MeSH terms
- Adrenal Glands, Adrenocorticotropic Hormone, Animals, Anxiety, Body Weight, Corticosterone, Dexamethasone, Glucocorticoids, Male, Mice, Inbred C57BL, Organ Size, Physical Conditioning, Animal, Restraint, Physical, Reflex, Startle, Stress, Psychological, Thymus Gland, Time Factors, Mice, Sensory Gating
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
