The DOI matches its Crossref record; 486 of the 486 references it cites were found in a registry or an index.
Stressor Specificity of Central Neuroendocrine Responses: Implications for Stress-Related Disorders
Abstract
Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.
Overview
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
Verification
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?
In the citing paper
“The PVN is innervated by GABAergic AHA neurons implicated in glucocorticoid-induced negative feedback regulation of HPA axis function (Pacak and Palkovits, 2001; Herman et al., 2002).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Pacak and Palkovits, 2001
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.1.0389 · Cited by 7,541
Sapolsky, R. M. (2000) · Endocrine Reviews · doi:10.1210/er.21.1.55 · Cited by 7,533
Protective and Damaging Effects of Stress Mediators
McEwen, B. S. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801153380307 · Cited by 6,733 · cited 6×
“Sapolsky and co-workers (39 – 41) and McEwen et al. (42) introduced and discussed in great detail new aspects of stress in terms of its adverse effects on various brain regions, especially the hippocampus.”
BackgroundInfluentialSakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Williams, S. C., Richardson, J. A., Kozlowski, G. P., Wilson, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80949-6 · Cited by 5,501
Handbook of Chemical Neuroanatomy
Stern, C. D. (1986) · Neurochemistry International · doi:10.1016/0197-0186(86)90021-5 · Cited by 4,160
A Syndrome produced by Diverse Nocuous Agents
Selye, H. (1936) · Nature · doi:10.1038/138032a0 · Cited by 3,967
Physiological functions of glucocorticoids in stress and their relation to pharmacological actions
MUNCK, A., GUYRE, P. M., & HOLBROOK, N. J. (1984) · Endocrine Reviews · doi:10.1210/edrv-5-1-25 · Cited by 3,083
The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis
Chrousos, G. P. (1992) · JAMA · doi:10.1001/jama.1992.03480090092034 · Cited by 2,689
Endogenous Pain Control Systems: Brainstem Spinal Pathways and Endorphin Circuitry
Basbaum, A. I., & Fields, H. L. (1984) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.07.030184.001521 · Cited by 2,687
Flagged first, then by citations
Research works printed but not linked: 7
- Delgado, 1972, Dialytrode for long-term intravertebral perfusion in awake monkeys., Arch Int Pharmacodyn Ther, 198, 9
- Plotsky, 1985, Hypophysiotrophic regulation of adenohypophyseal adrenocorticotropin secretion., Fed Proc, 44, 207
- Brizzee, 1991, Role of vasopressin release in acutely altered baroreflex sensitivity during hemorrhage in rats, Am J Physiol, 261, R667
- Mezey, 1991, CRF-containing neurons in the hypothalamic paraventricular nucleus: Regulation, especially by catecholamines., Front Neuroendocrinol, 12, 23
- Záborszky, 1979, Afferent brain stem connections of the central amygdaloid nucleus., Verh Anat Ges, 73, 1117
- Chrousos, 1997, The neuroendocrinology of stress: its relation to the hormonal milieu, growth, and development., Growth Genet Horm, 13, 1
- Hyman, 1998, Brain neurocircuitry of anxiety and fear: implications for clinical research and practice., Biol Psychiat, 44, 1201
Cited by
Sorted by citations
Parent, A.-S., Teilmann, G., Juul, A., Skakkebaek, N. E., Toppari, J., & Bourguignon, J.-P. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0019 · Cited by 1,762
Herman, J. P., Figueiredo, H., Mueller, N. K., Ulrich-Lai, Y., Ostrander, M. M., Choi, D. C., & Cullinan, W. E. (2003) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2003.07.001 · Cited by 1,586
Timing of pubertal maturation in girls: an integrated life history approach
Ellis, B. J. (2004) · Psychological Bulletin · doi:10.1037/0033-2909.130.6.920 · Cited by 1,014
Hair cortisol, stress exposure, and mental health in humans: A systematic review
Staufenbiel, S. M., Penninx, B. W. J. H., Spijker, A. T., Elzinga, B. M., & van Rossum, E. F. C. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.11.015 · Cited by 736
Gillies, G. E., & McArthur, S. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002071 · Cited by 733
The brain and the stress axis: the neural correlates of cortisol regulation in response to stress
Dedovic, K., Duchesne, A., Andrews, J., Engert, V., & Pruessner, J. C. (2009) · NeuroImage · doi:10.1016/j.neuroimage.2009.05.074 · Cited by 699
Mather, M., Clewett, D., Sakaki, M., & Harley, C. W. (2016) · Behavioral and Brain Sciences · doi:10.1017/s0140525x15000667 · Cited by 695
Kalmbach, D. A., Anderson, J. R., & Drake, C. L. (2018) · Journal of Sleep Research · doi:10.1111/jsr.12710 · Cited by 620
“Indeed, the differential resilience of various psychoneurobiological systems to the ravages of stress exposure moderates vulnerability to many medical and psychological illnesses (Kobasa, Maddi, & Courington, 1981; Pacak & Palkovits, 2001; Selye, 1985).”
BackgroundCatecholaminergic systems in stress: structural and molecular genetic approaches
Kvetnansky, R., Sabban, E. L., & Palkovits, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00042.2006 · Cited by 548
Self-citationEarly programming of the hypothalamo–pituitary–adrenal axis
MATTHEWS, S. (2002) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(02)00690-2 · Cited by 513
Measurement of Immediate‐Early Gene Activation‐ c‐fos and Beyond
Kovács, K. J. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01734.x · Cited by 493
Early life stress and development: potential mechanisms for adverse outcomes
Smith, K. E., & Pollak, S. D. (2020) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-020-09337-y · Cited by 500
Engelmann, M., Landgraf, R., & Wotjak, C. T. (2004) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2004.09.001 · Cited by 450
Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit
Anthony, T. E., Dee, N., Bernard, A., Lerchner, W., Heintz, N., & Anderson, D. J. (2014) · Cell · doi:10.1016/j.cell.2013.12.040 · Cited by 310
Resstel, L. B. M., Tavares, R. F., Lisboa, S. F. S., Joca, S. R. L., Corrêa, F. M. A., & Guimarães, F. S. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00046.x · Cited by 283
Ventral tegmental area dopamine revisited: effects of acute and repeated stress
Holly, E. N., & Miczek, K. A. (2016) · Psychopharmacology · doi:10.1007/s00213-015-4151-3 · Cited by 265
Effects of Chronic Social Stress on Obesity
Scott, K. A., Melhorn, S. J., & Sakai, R. R. (2012) · Current Obesity Reports · doi:10.1007/s13679-011-0006-3 · Cited by 251
Steroids, neuroactive steroids and neurosteroids in psychopathology
Dubrovsky, B. O. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.11.001 · Cited by 250
Stressor-specific alterations in corticosterone and immune responses in mice
Bowers, S. L., Bilbo, S. D., Dhabhar, F. S., & Nelson, R. J. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.07.012 · Cited by 222
The molecular physiology of CRH neurons
Aguilera, G., & Liu, Y. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2011.08.002 · Cited by 198
Kinsey‐Jones, J. S., Li, X. F., Knox, A. M. I., Wilkinson, E. S., Zhu, X. L., Chaudhary, A. A., Milligan, S. R., Lightman, S. L., & O’Byrne, K. T. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01807.x · Cited by 196
Gene networks specific for innate immunity define post-traumatic stress disorder
Breen, M. S., Maihofer, A. X., Glatt, S. J., Tylee, D. S., Chandler, S. D., Tsuang, M. T., Risbrough, V. B., Baker, D. G., O'Connor, D. T., Nievergelt, C. M., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.9 · Cited by 180
Nair, A., Vadodaria, K. C., Banerjee, S. B., Benekareddy, M., Dias, B. G., Duman, R. S., & Vaidya, V. A. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301276 · Cited by 189
Effects of stressors on the behavior and physiology of domestic cats
Stella, J., Croney, C., & Buffington, T. (2013) · Applied Animal Behaviour Science · doi:10.1016/j.applanim.2012.10.014 · Cited by 181
Disconnection and reconnection: The morphological basis of (mal)adaptation to stress
Sousa, N., & Almeida, O. F. X. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.08.006 · Cited by 159
Limbic and HPA axis function in an animal model of chronic neuropathic pain
Ulrich-Lai, Y. M., Xie, W., Meij, J. T. A., Dolgas, C. M., Yu, L., & Herman, J. P. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.03.012 · Cited by 146
Single nucleotide polymorphisms related to hpa axis reactivity
DeRijk, R. H. (2009) · NeuroImmunoModulation · doi:10.1159/000216192 · Cited by 140
Valenti, O., Gill, K. M., & Grace, A. A. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2012.08038.x · Cited by 131
Stress-induced increase of testosterone: contributions of social status and sympathetic reactivity
Chichinadze, K., & Chichinadze, N. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.03.020 · Cited by 126
Biomarkers of stress in behavioural medicine
Nater, U. M., Skoluda, N., & Strahler, J. (2013) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e328363b4ed · Cited by 125
REM Sleep Rebound as an Adaptive Response to Stressful Situations
Suchecki, D., Tiba, P. A., & Machado, R. B. (2012) · Frontiers in Neurology · doi:10.3389/fneur.2012.00041 · Cited by 119
Psychobiology of childhood maltreatment: effects of allostatic load?
Grassi-Oliveira, R., Ashy, M., & Stein, L. M. (2008) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462008000100012 · Cited by 116
Glucocorticoid sensitivity in humans-interindividual differences and acute stress effects
Rohleder, N., Wolf, J. M., & Kirschbaum, C. (2003) · Stress · doi:10.1080/1025389031000153658 · Cited by 118
DeRijk, R. H., van Leeuwen, N., Klok, M. D., & Zitman, F. G. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.03.012 · Cited by 117
Age-Dependent and Gender-Dependent Regulation of Hypothalamic-Adrenocorticotropic-Adrenal Axis
Veldhuis, J. D., Sharma, A., & Roelfsema, F. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.02.002 · Cited by 110
Toward understanding the impact of trauma on the early developing human brain
Thomason, M. E., & Marusak, H. A. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2016.02.022 · Cited by 101
de Vente, W., van Amsterdam, J. G. C., Olff, M., Kamphuis, J. H., & Emmelkamp, P. M. G. (2015) · BioMed Research International · doi:10.1155/2015/431725 · Cited by 90
Bohringer, A., Schwabe, L., Richter, S., & Schachinger, H. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.08.002 · Cited by 89
Neonatal maternal separation enhances central sensitivity to noxious colorectal distention in rat
Chung, E. K. Y., Zhang, X., Li, Z., Zhang, H., Xu, H., & Bian, Z. (2007) · Brain Research · doi:10.1016/j.brainres.2007.03.047 · Cited by 86
Ruscio, M. G., Sweeny, T., Hazelton, J., Suppatkul, P., & Sue Carter, C. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.08.004 · Cited by 81
Interaction of Stress, Corticotropin-Releasing Factor, Arginine Vasopressin and Behaviour
Beurel, E., & Nemeroff, C. B. (2014) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2014_306 · Cited by 64
“(Dayas et al. 2001; Pacak and Palkovits 2001).”
BackgroundMitchell, J. C., Li, X. F., Breen, L., Thalabard, J.-C., & O’Byrne, K. T. (2005) · Endocrinology · doi:10.1210/en.2004-1053 · Cited by 58
Jaimes-Hoy, L., Joseph-Bravo, P., & de Gortari, P. (2008) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.11.003 · Cited by 51
Effects of chronic stress on the onset and progression of Huntington’s disease in transgenic mice
Mo, C., Renoir, T., & Hannan, A. J. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.07.008 · Cited by 46
Liu, X., Wellman, L. L., Yang, L., Ambrozewicz, M. A., Tang, X., & Sanford, L. D. (2011) · Sleep · doi:10.5665/sleep.1394 · Cited by 35
de Gortari, P., Mancera, K., Cote-Vélez, A., Amaya, M. I., Martínez, A., Jaimes-Hoy, L., & Joseph-Bravo, P. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.09.010 · Cited by 33
Apfel, B. A., Otte, C., Inslicht, S. S., McCaslin, S. E., Henn-Haase, C., Metzler, T. J., Makotkine, I., Yehuda, R., Neylan, T. C., & Marmar, C. R. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.11.016 · Cited by 27
Gomes, F. V., Alves, F. H. F., Guimarães, F. S., Correa, F. M. A., Resstel, L. B. M., & Crestani, C. C. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.09.007 · Cited by 27
Effects of Novelty Stress on Hippocampal Gene Expression, Corticosterone and Motor Activity in Mice
Kurumaji, A., Umino, M., & Nishikawa, T. (2011) · Neuroscience Research · doi:10.1016/j.neures.2011.06.006 · Cited by 18
He, F., Ai, H., Wang, M., Wang, X., & Geng, X. (2018) · Neuroscience Bulletin · doi:10.1007/s12264-018-0282-y · Cited by 15
Sirivelu, M. P., MohanKumar, P. S., & MohanKumar, S. M. J. (2012) · Life Sciences · doi:10.1016/j.lfs.2012.09.004 · Cited by 14
Metadata
- Authors
- Pacák, K., & Palkovits, M.
- Affiliations
- Pediatric and Reproductive Endocrinology Branch (K.P.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
- Laboratory of Genetics (M.P.), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1583
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2001-08-01
- Volume
- 22
- Issue
- 4
- Pages
- 502-548
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2066156347
- Cited by
- 926
- References
- 486
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 21 · 2023: 24 · 2022: 23 · 2021: 26 · 2020: 28 · 2019: 24 · 2018: 38 · 2017: 27 · 2016: 36 · 2015: 47 · 2014: 45 · 2013: 39 · 2012: 56
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Child Health and Human Development
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- stressor specificity, neuroendocrine response, stress-related disorders, sympathoadrenal system, hypothalamic-pituitary-adrenal axis, Fos-like immunoreactivity, restraint stress, hemorrhage, cold exposure, pain, hypoglycemia
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Brain, Humans, Hypothalamo-Hypophyseal System, Neurosecretory Systems, Paraventricular Hypothalamic Nucleus, Stress, Physiological
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
