Post-stress recovery of pituitary–adrenal hormones and glucose, but not the response during exposure to the stressor, is a marker of stress intensity in highly stressful situations

doi:10.1016/S0006-8993(01)03112-2

Brain Research

Volume 926, Issues 1–2, 1 February 2002, Pages 181-185

https://doi.org/10.1016/S0006-8993(01)03112-2 Get rights and content

Abstract

Acute immobilization in male rats elicited the same ACTH, corticosterone and glucose response as foot shock when measured immediately after stress. However, post-stress recovery of plasma ACTH, corticosterone and glucose levels were delayed in immobilized versus shocked rats. Similarly, stress-induced anorexia was much greater in the former animals. All these data suggest that post-stress speed of recovery of some physiological variables is positively related to stressor intensity and could be used to evaluate it.

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Acknowledgements

This work was supported by DGICYT (PM98-0175) and CUR (1999SGR-330) Grants. CM is a fellow of the Universitat Autònoma de Barcelona. We are very grateful to Dr. W.C. Engeland (Department of Surgery, University of Minnesota, Minneapolis, USA) for his gift of the ACTH antiserum and to Dr. A.F. Parlow (NIDDK National Hormone and Peptide Program, California, USA) for his gift of the prolactin standard and antiserum.

References (20)

A. Armario et al.
Influence of various acute stressors on the activity of adult male rats in a holeboard and in the forced swim test
Pharmacol. Biochem. Behav.
(1991)
A. Armario et al.
Sensitivity of anterior pituitary hormones to graded levels of psychological stress
Life Sci.
(1986)
A. Armario et al.
The serum glucose response to acute stress is sensitive to the intensity of the stressor and to habituation
Psychoneuroendocrinology
(1990)
A. Armario et al.
Sensitivity of corticosterone and some metabolic variables to graded levels of low intensity stresses in adult male rats
Physiol. Behav.
(1986)
S.F. De Boer et al.
Plasma catecholamine, corticosterone and glucose responses to repeated stress in rats: effect of interstressor interval length
Physiol. Behav.
(1990)
A. Garcı́a et al.
Individual differences in the recovery of the hypothalamic–pituitary–adrenal axis after termination of the exposure to severe stressor in outbred male Sprague–Dawley rats
Psychoneuroendocrinology
(2001)
M.B. Hennessy et al.
Sensitive pituitary–adrenal responsiveness to varying intensities of psychological stimulation
Physiol. Behav.
(1978)
O. Martı́ et al.
Effects of chronic stress on food intake in rats: influence of stressor intensity and duration of daily exposure
Physiol. Behav.
(1994)
B.H. Natelson et al.
Adrenal hormonal indices of stress in laboratory rats
Physiol. Behav.
(1987)
B.H. Natelson et al.
Humoral indices of stress in rats
Physiol. Behav.
(1981)

There are more references available in the full text version of this article.

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Animal models of PTSD: Comparison of the neuroendocrine and behavioral sequelae of immobilization and a modified single prolonged stress procedure that includes immobilization
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A single exposure to some stressors results in long-lasting consequences reminiscent of those found in post-traumatic stress disorder (PTSD), but results are very often controversial. Although there is no consensus regarding the best animal models of PTSD, the single prolonged stress (SPS) model, consisting of sequential exposure within the same day to various stressors (typically restraint, forced swim, and ether), has gained acceptance. However, results, particularly those related to the hypothalamic-pituitary-adrenal (HPA) axis, are inconsistent and there is no evidence that SPS is clearly distinct from models using a single severe stressor. In the present study, we compared in male rats the behavioral and neuroendocrine (HPA) consequences of exposure to immobilization on boards (IMO) with a SPS-like model (SPSi) in which IMO and isoflurane were substituted for restraint and ether, respectively. Both procedures caused a similar impact on food intake and body weight as well as on sensitization of the HPA response to a novel environment (hole-board) on the following day. Reduction of activity/exploration in the hole-board was also similar with both stressors, although the impact of sudden noise was higher in SPSi than IMO. Neither IMO nor SPSi significantly affected contextual fear conditioning acquisition, although a similar trend for impaired fear extinction was observed compared to controls. Exposure to additional stressors in the SPSi did not interfere with homotypic adaptation of the HPA axis to IMO. Thus, only modest neuroendocrine and behavioral differences were observed between IMO and SPSi and more studies comparing putative PTSD models are needed.
Individual differences in the neuroendocrine response of male rats to emotional stressors are not trait-like and strongly depend on the intensity of the stressors
2021, Psychoneuroendocrinology
Citation Excerpt :
If there is no consistent individual HPA response across different types of emotional stressors and that response is critically dependent on the particular stressful situation, this inconsistency could at least in part explain the controversial results regarding HPA activity and particular behavioral traits (Armario and Nadal, 2013). Therefore, the aim of the present work was to characterize the correlation of individual differences in the response of adult male rats to a set of predominantly stressors chosen because there is evidence that they greatly differ in nature and intensity on the basis of well-known biological indexes, including HPA hormones, prolactin and food intake (Belda et al., 2016; Márquez et al., 2002; Pace et al., 2005; Rabasa et al., 2015; Rotllant et al.,2007), all of them good markers of stressor intensity in animals and humans (Armario et al., 2020). Male Sprague–Dawley rats obtained from the breeding centre of the Universitat Autònoma de Barcelona were used.
Biological response to stressors is critical to understand stress-related pathologies and vulnerability to psychiatric diseases. It is assumed that we can identify trait-like characteristics in biological responsiveness by testing subjects in a particular stressful situation, but there is scarce information on this issue. We then studied, in a normal outbred population of adult male rats (n = 32), the response of well-characterized stress markers (ACTH, corticosterone and prolactin) to different types of stressors: two novel environments (open-field, OF1 and OF2), an elevated platform (EP), forced swim (SWIM) and immobilization (IMO). Based on both plasma ACTH and prolactin levels, the OF1 was the lowest intensity situation, followed by the OF2 and the EP, then SWIM and finally IMO. When correlations between the individual responses to the different stressors were studied, the magnitude of the correlations was most dependent on the similarities in intensity rather than on other characteristics of stressors, with good correlations between similar intensity stressors and no correlations at all were found between stressors markedly differing in intensity. In two additional confirmatory experiments (n = 37 and n = 20) with HPA hormones, we observed good correlation between the response to restraint and IMO, which were close in intensity, and no correlation between OF1 and SWIM. The present results suggest that individual neuroendocrine response to a particular stressor does not predict the response to another stressor greatly differing in intensity, thus precluding characterization of low or high responsive individuals to any stressor in a normal population. The present data have important implications for human studies.
Acute exposure of rats to a severe stressor alters the circadian pattern of corticosterone and sensitizes to a novel stressor: Relationship to pre-stress individual differences in resting corticosterone levels
2020, Hormones and Behavior
Traumatic events have been proposed to be associated with hypo-activity of the hypothalamic-pituitary-adrenal (HPA) axis, but data in animal models exposed to severe stressors are controversial and have important methodological concerns. Individual differences in resting or stress levels of corticosterone might explain some of the inconsistencies. We then studied this issue in male rats exposed to 2 h immobilization on boards (IMO), a severe stressor.
Thirty-six rats were blood sampled under resting conditions four times a day on three non-consecutive days. Then, they were assigned to control (n = 14) or IMO (n = 22) to study the HPA response to IMO, the stressor-induced alterations in the circadian pattern of corticosterone (CPCORT), and the behavioral and HPA responsiveness to an open-field.
Individual differences in pre-IMO resting corticosterone were inconsistent, but averaging data markedly improved consistency. The CPCORT was markedly altered on day 1 post-IMO (higher trough and lower peak levels), less altered on day 3 and apparently normal on day 7. Importantly, when rats were classified in low and high resting corticosterone groups (LCORT and HCORT, respectively), on the basis of the area under the curve (AUC) of the averaged pre-IMO data, AUC differences between LCORT and HCORT groups were maintained in controls but disappeared in IMO rats during the post-IMO week. Open-field hypo-activity and corticosterone sensitization were similar in LCORT and HCORT groups nine days after IMO. A single IMO exposure causes long-lasting HPA alterations, some of them dependent on pre-stress resting corticosterone levels, with no evidence for post-IMO resting corticosterone hypo-activity.
Focusing attention on biological markers of acute stressor intensity: Empirical evidence and limitations
2020, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Therefore, plasma corticosterone is exquisitely sensitive to moderate increases in plasma ACTH but did not reflect greater increases in ACTH unless the post-stress period is evaluated. Thus, when comparing exposure to high intensity foot-shocks and IMO, various classical biological markers (ACTH, corticosterone and prolactin) were unable to distinguish between the two stressors when measured just after it, but clear differences emerged among all variables during the post-stress period, indicating that IMO was clearly more severe than foot-shock (Marquez et al., 2002). Despite these well-established facts, most studies in the field of stress with laboratory animals still rely on plasma corticosterone measurement just after the stressor, what can lead to erroneous conclusions in most cases if the challenging stressor is not of low intensity.
ARMARIO, A, J. Labad and R. Nadal. Focusing attention on biological markers of acute stressor intensity: empirical evidence and limitations. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS. The availability of biological markers that objectively quantify stress is a highly relevant issue. However, experimental evidence suggests that most physiological changes elicited by emotional stressors do not reflect their intensity and are not useful for this purpose. Thus, we review experimental evidence in animals and humans about the putative validity of neuroendocrine and sympathetic/parasympathetic variables to measure stress. Plasma levels of some hormones (e.g. ACTH, glucocorticoids, prolactin and catecholamines) have been found to reflect, at least under certain conditions, the intensity of emotional stressors in animals and probably in humans. However, the temporal resolution of hormone changes is insufficient to reflect the very dynamic psychological processes taking place while experiencing stressors. Cardiovascular parameters (e.g. heart rate and blood pressure) have much better temporal resolution but their validity as markers of stressor intensity either in animals or humans is problematic. Skin conductance and pupil dilation appear to be promising. Additional and more systematic studies are needed to demonstrate the actual validity of stress-induced physiological changes to quantify stress.
Neuroprotective offerings by agmatine
2019, NeuroToxicology
Agmatine, an endogenous polyamine in CNS, is derived from arginine by dearboxylation. Like polyamines, agmatine has been studied for its neuroprotetive effects. At present, a large body of experimental evidences has been gathered that demonstrate the neuroprotective effects of agmatine. The neuroprotective effects have been observed in various CNS cell lines and animal models against the excitotocity, oxidative damage, corticosteroidid induced neurotoxicity, ischemic/hypoxic or oxygen-glucose deprivation toxicity, spinal cord injury and traumatic brain injury. The studies have been extended to rescue of retinal ganglion cells from toxicities. The mechanistic studies suggest that neuroprotection offered by agmatine can be assigned to its multimolecular biological effects. These include its action as glutamatergic receptor antagonist, α₂-adrenoceptor agonist, imidazoline binding site ligand, NOS inhibitor, ADP ribosylation inhibitor, and blocker of ATP-sensitive potassium and voltage-gated calcium channels, anti-apoptotic and antioxidant. Its action as regulator for polyamine synthesis, insulin release assists the neuroprotection.
The cumulative evidences of preclinical studies support the possible use of agmatine as an agent for neuronal damage and neurodegenerative diseases. However, it will be hasty to assert and promote agmatine as a novel therapeutic agent for neuroprotection. The review is focused on the role of agmatine in different types and mechanisms of neural injuries. The aspects of concern like dose range, pharmacokinetics of exogenous agmatine, levels of endogenous agmatine during events of injury etc. has to be addressed.
Expression of the PPM1F Gene Is Regulated by Stress and Associated With Anxiety and Depression
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Molecular mechanisms underlying psychological sequelae of exposure to stressful experiences, such as posttraumatic stress disorder (PTSD) and depression, are not well understood.
Using convergent evidence from animal and human transcriptomic and genomic studies, we aimed to identify genetic mechanisms underlying depression and anxiety after traumatic experiences.
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Taken together, our data suggest a mechanistic pathway involving PPM1F and CAMK2G in stress- and trauma-related manifestation of anxiety and depression across species.

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Short communicationPost-stress recovery of pituitary–adrenal hormones and glucose, but not the response during exposure to the stressor, is a marker of stress intensity in highly stressful situations

Abstract

Section snippets

Acknowledgements

Pharmacol. Biochem. Behav.

Life Sci.

Psychoneuroendocrinology

Physiol. Behav.

Physiol. Behav.

Psychoneuroendocrinology

Physiol. Behav.

Physiol. Behav.

Physiol. Behav.

Physiol. Behav.

Short communication
Post-stress recovery of pituitary–adrenal hormones and glucose, but not the response during exposure to the stressor, is a marker of stress intensity in highly stressful situations