scholarly journals Corticosterone Can Act at the Posterior Paraventricular Thalamus to Inhibit Hypothalamic-Pituitary-Adrenal Activity in Animals that Habituate to Repeated Stress

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4917-4930 ◽  
Author(s):  
Azra Jaferi ◽  
Seema Bhatnagar

Glucocorticoids released by stress bind to glucocorticoid (GR) and/or mineralocorticoid receptors (MR) to exert negative feedback of subsequent hypothalamic-pituitary-adrenal (HPA) responses to stress. Feedback inhibition is implicated in habituation of HPA activity to repeated exposure to the same (homotypic) stressor. We hypothesized that the posterior paraventricular thalamus (pPVTh) is a site where corticosterone acts to exert negative feedback during repeated stress and that is important for habituation. As previously reported, the pPVTh inhibits HPA responses to homotypic and heterotypic stressors in repeatedly, but not acutely, stressed rats. We conducted a series of experiments involving intra-pPVTh administration of MR and/or GR agonists or antagonists during different time frames over 8 d of restraint. MR exist in the pPVTh, as do GR as shown by our immunocytochemical results. Acute intra-pPVTh injection of MR and/or GR antagonist before the eighth restraint did not alter expression of habituation. Because habituation may develop before d 8, we manipulated GR and MR in the pPVTh throughout 8 d of stress using intra-pPVTh corticosterone implants, which enhanced habituation on d 8 without affecting acute stress responses. Conversely, daily intra-pPVTh injections of GR and MR antagonists on d 1–7 of restraint prevented habituation on d 8. These data suggest that corticosterone released during repeated stress can act at GR and MR in the pPVTh to inhibit HPA responses to homotypic stress. We also found that some GR-containing cells in the pPVTh project to the medial prefrontal cortex and basolateral amygdala, suggesting that pPVTh-induced inhibition of HPA activity is potentially mediated by its projections to these select limbic structures.

2013 ◽  
Vol 16 (9) ◽  
pp. 2013-2025 ◽  
Author(s):  
Kathryn M. Gill ◽  
Anthony A. Grace

Abstract The basolateral amygdala (BLA) and ventral subiculum (vSub) of the hippocampus convey emotion and context information, respectively, to the nucleus accumbens (NAc). Using in vivo extracellular recordings from NAc neurons, we examined how acute and repeated restraint stress alters the plasticity of the vSub and BLA afferent pathways. High-frequency (HFS) and low-frequency (LFS) stimulation was applied to the vSub to assess the impact on NAc responses to vSub and BLA inputs. In addition, iontophoretic application of the dopamine D2-antagonist sulpiride was used to explore the role of dopamine in the NAc in mediating the effects of stress on plasticity. Acute and repeated restraint caused disparate effects on BLA- and vSub-evoked responses in the NAc. Following repeated restraint, but not after acute restraint, HFS of the vSub failed to potentiate the vSub–NAc pathway while instead promoting a long-lasting reduction of the BLA–NAc pathway and these effects were independent of D2-receptor activity. In contrast, LFS to the vSub pathway after acute restraint resulted in potentiation in the vSub–NAc pathway while BLA-evoked responses were unchanged. When sulpiride was applied prior to LFS of the vSub after acute stress, there was a pronounced decrease in vSub-evoked responses similar to control animals. This work provides new insight into the impact of acute and repeated stress on the integration of context and emotion inputs in the NAc. These data support a model of stress whereby the hippocampus is inappropriately activated and dominates the information processing within this circuit via a dopaminergic mechanism after acute bouts of stress.


Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4811-4819 ◽  
Author(s):  
Nathan K. Evanson ◽  
Jeffrey G. Tasker ◽  
Matthew N. Hill ◽  
Cecilia J. Hillard ◽  
James P. Herman

Glucocorticoid hormones are secreted in response to stimuli that activate the hypothalamo-pituitary-adrenocortical (HPA) axis and self-regulate through negative feedback. Negative feedback that occurs on a rapid time scale is thought to act through nongenomic mechanisms. In these studies, we investigated fast feedback inhibition of HPA axis stress responses by direct glucocorticoid action at the paraventricular nucleus of the hypothalamus (PVN). Local infusion of dexamethasone or a membrane-impermeant dexamethasone-BSA conjugate into the PVN rapidly inhibits restraint-induced ACTH and corticosterone release in a manner consistent with feedback actions at the cell membrane. The dexamethasone fast feedback response is blocked by the cannabinoid CB1 receptor antagonist AM-251, suggesting that fast feedback requires local release of endocannabinoids. Hypothalamic tissue content of the endocannabinoid 2-arachidonoyl glycerol is elevated by restraint stress, consistent with endocannabinoid action on feedback processes. These data support the hypothesis that glucocorticoid-induced fast feedback inhibition of the HPA axis is mediated by a nongenomic signaling mechanism that involves endocannabinoid signaling at the level of the PVN.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leonardo Santana Novaes ◽  
Letícia Morais Bueno-de-Camargo ◽  
Carolina Demarchi Munhoz

AbstractThe persistence of anxiety and the deficit of fear memory extinction are both phenomena related to the symptoms of a trauma-related disorder, such as post-traumatic stress disorder (PTSD). Recently we have shown that single acute restraint stress (2 h) in rats induces a late anxiety-related behavior (observed ten days after stress), whereas, in the present work, we found that the same stress impaired fear extinction in animals conditioned ten days after stress. Fourteen days of environmental enrichment (EE) prevented the deleterious effect of stress on fear memory extinction. Additionally, we observed that EE prevented the stress-induced increase in AMPA receptor GluA1 subunit phosphorylation in the hippocampus, but not in the basolateral amygdala complex and the frontal cortex, indicating a potential mechanism by which it exerts its protective effect against the stress-induced behavioral outcome.


1997 ◽  
Vol 65 (5) ◽  
pp. 360-368 ◽  
Author(s):  
Firdaus S. Dhabhar ◽  
Bruce S. McEwen ◽  
Robert L. Spencer

2021 ◽  
Vol 11 (4) ◽  
pp. 508
Author(s):  
Michael Schaefer ◽  
Julian Hellmann-Regen ◽  
Sören Enge

Stress belongs to the most frequent negative feelings people are confronted with in daily life. Strategies against acute stress include, e.g., relaxation techniques or medications, but it is also known that placebos can successfully reduce negative emotional stress. While it is widely held that placebos require deception to provoke a response, recent studies demonstrate intriguing evidence that placebos may work even without concealment (e.g., against anxiety or pain). Most of these studies are based on self-report questionnaires and do not include physiological measures. Here we report results of a study examining whether placebos without deception reduce acute stress. A total of 53 healthy individuals received either placebos without deception or no pills before participating in a laboratory stress test (Maastricht Acute Stress Test, MAST). We recorded self-report stress measures and cortisol responses before and after the MAST. Results showed no significant differences between the placebo and the control group, but when comparing participants with high relative to low beliefs in the power of placebos we found significant lower anxiety and cortisol responses for the placebo believers. These results show that non-deceptive placebos may successfully reduce acute anxiety and stress, but only in participants who had a strong belief in placebos. We discuss the results by suggesting that open-label placebos might be a possible treatment to reduce stress at least for some individuals.


2008 ◽  
Vol 68 (4) ◽  
pp. 572-578 ◽  
Author(s):  
R H Straub ◽  
G Pongratz ◽  
H Hirvonen ◽  
T Pohjolainen ◽  
M Mikkelsson ◽  
...  

Objective:Acute stress in patients with rheumatoid arthritis (RA) should stimulate a strong stress response. After cryotherapy, we expected to observe an increase of hormones of the adrenal gland and the sympathetic nervous system.Methods:A total of 55 patients with RA were recruited for whole-body cryotherapy at −110°C and −60°C, and local cold therapy between −20°C and −30°C for 7 days. We measured plasma levels of steroid hormones, neuropeptide Y (sympathetic marker), and interleukin (IL)6 daily before and after cryotherapy.Results:In both therapy groups with/without glucocorticoids (GC), hormone and IL6 levels at baseline and 5 h after cold stress did not change over 7 days of cryotherapy. In patients without GC, plasma levels of cortisol and androstenedione were highest after −110°C cold stress followed by −60°C or local cold stress. The opposite was found in patients under GC therapy, in whom, unexpectedly, −110°C cold stress elicited the smallest responses. In patients without GC, adrenal cortisol production increased relative to other adrenal steroids, and again the opposite was seen under GC therapy with a loss of cortisol and an increase of dehydroepiandrosterone. Importantly, there was no sympathetic stress response in both groups. Patients without GC and −110°C cold stress demonstrated higher plasma IL6 compared to the other treatment groups (not observed under GC), but they showed the best clinical response.Conclusions:We detected an inadequate stress response in patients with GC. It is further shown that the sympathetic stress response was inadequate in patients with/without GC. Paradoxically, plasma levels of IL6 increased under strong cold stress in patients without GC. These findings confirm dysfunctional stress axes in RA.


Animals ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 175 ◽  
Author(s):  
Pfunzo Muvhali ◽  
Maud Bonato ◽  
Anel Engelbrecht ◽  
Irek Malecki ◽  
Denise Hough ◽  
...  

The effect of extensive human presence and regular gentle handling performed at an early age (0–3 months old) on stress responses and reactivity of juvenile ostriches towards humans was investigated. A total of 416 ostrich chicks over two years were exposed to one of three treatments for three months after hatching; namely, Human Presence 1 (HP1, N = 144): extensive/prolonged human presence with physical contact (touch, stroking), gentle human voice, and visual stimuli; Human Presence 2 (HP2, N = 136): extensive/prolonged human presence without physical contact, but with gentle human voice and visual stimuli; and the Standard treatment (S, N = 136): human presence limited to routine feed and water supply as a control. At 7.5 months of age, the plasma heterophil/lymphocyte (H/L) ratio was measured before and 72 h after feather harvesting and feather clipping to determine acute stress responses, while chronic stress was measured by quantification of corticosterone (CORT) concentrations in the floss feathers of the birds. Birds’ behavioural response towards a familiar or an unfamiliar handler was evaluated at 12 months using docility and fear tests, and through behavioural observations conducted on random days between the ages of 8–13 months. Willingness to approach, and to allow touch interactions, aggressiveness, and exhibition of sexual display towards the handler, was recorded. No difference in the H/L ratios before and after feather harvesting and clipping was observed in HP1 birds, whereas H/L ratios showed a significant increase 72 h post feather harvesting and clipping in HP2 and S birds (p < 0.05). Birds from the S treatment exhibited a significantly (p < 0.05) higher feather CORT concentration compared with HP1 birds, while HP2 birds had intermediate responses. Birds’ reactivity towards humans and temperament as evaluated using behavioural observations, docility, and fear tests was not affected by treatment (p > 0.05). However, HP1 and HP2 birds were more inclined (p < 0.05) to approach a familiar rather than an unfamiliar handler during the behavioural observations, indicating an ability to distinguish between a familiar and an unfamiliar handler. Overall, the results indicate that early gentle human interactions with ostrich chicks can be beneficial in reducing physiological stress sensitivity later in life and facilitate the ability of ostriches to distinguish between familiar and unfamiliar handlers.


2008 ◽  
Vol 78 (4) ◽  
pp. 423-429 ◽  
Author(s):  
Leanna Isserlin ◽  
Gadi Zerach ◽  
Zahava Solomon

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