scholarly journals Residual avoidance: a new consistent and repeatable readout of chronic stress-induced conflict anxiety reversible by antidepressant treatment

2018 ◽  
Author(s):  
Thomas D. Prevot ◽  
Keith A. Misquitta ◽  
Corey Fee ◽  
Dwight F. Newton ◽  
Dipashree Chatterjee ◽  
...  

AbstractStress-related illnesses such as major depressive and anxiety disorders are characterized by maladaptive responses to stressful life events. Chronic stress-based animal models have provided critical insight into the understanding of these responses. Currently available assays measuring chronic stress-induced behavioral states in mice are limited in their design (short, not repeatable, sensitive to experimenter-bias) and often inconsistent. Using the Noldus PhenoTyper apparatus, we identified a new readout that repeatedly assesses behavioral changes induced by chronic stress in two mouse models i.e. chronic restraint stress (CRS) and chronic unpredictable mild stress (UCMS). The PhenoTyper test consists of overnight monitoring of animals’ behavior in home-cage setting before, during and after a 1hr light challenge applied over a designated food zone. We tested the reproducibility and reliability of the PhenoTyper test in assessing the effects of chronic stress exposure, and compared outcomes with commonly-used tests. While chronic stress induced heterogeneous profiles in classical tests, CRS- and UCMS-exposed mice showed a very consistent response in the PhenoTyper test. Indeed, CRS and UCMS mice continue avoiding the lit zone in favor of the shelter zone. This “residual avoidance” after the light challenge, lasted for hours beyond termination of the challenge, was not observed after acute stress and was consistently found throughout stress exposure in both models. Chronic stress-induced residual avoidance was alleviated by chronic imipramine treatment but not acute diazepam administration. This behavioral index should be instrumental for studies aiming to better understand the trajectory of chronic stress-induced deficits and potentially screen novel anxiolytics and antidepressants.

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Christine Fahrngruber ◽  
Kalina Duszka ◽  
Jürgen König

AbstractChronic stress is associated with impacting eating behavior, namely food choice and energy intake, with a shift towards more palatable and energy dense foods. Additionally, eating behavior is influenced by other psychological factors like mood and emotions. The categorization of people into eating types such as restrained, emotional, and external eaters has gained attraction. Reported changes in eating behavior due to psychological stress are only occasionally accompanied by measures of physiological hunger through ghrelin. The primary objective of this study was to investigate how chronic stress and acute cortisol reactivity affect active ghrelin secretion and how these outcomes account for different eating types. 16 healthy, young males (age: 23 ± 3 years, BMI: 22.5 ± 1.3kg/m2) with low (n = 8) and average-to-high (n = 8) chronic stress level were subjected to the Trier Social Stress Test (TSST) and a control version on two separate days. Active ghrelin, cortisol, glucose, and heart rate were measured throughout the test. Subjects rated their hunger by means of visual analog scale and current mood was assessed with the Positive and Negative Affect Scale (PANAS). In addition, participants filled out the Dutch Eating Behavior Questionnaire (DEBQ) to account for their subjective eating behavior. Overall ghrelin values where higher on the test day compared to the control day. Ghrelin values were also higher during the time leading up to the stress or control test (TSST) than during the conclusion of said tests. On both days, mean values for active ghrelin where higher in individuals with low chronic stress exposure compare to those with average-to-high chronic stress exposure. While values from test to control day decreased for lower stressed participants, they slightly increased for higher stressed participants. Cortisol responders displayed higher ghrelin values on test day than cortisol non-responders, but this association inverted for the control day. Results indicate that chronic stress influences acute stress response and further alters active ghrelin production, which in turn can influence eating behavior. Replication in a greater group of participants of differing weight and sex could yield a greater understanding of stress induced eating. Factors such as relaxation techniques and coping mechanisms could further improve our knowledge and evaluate treatment possibilities.


Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2942-2952 ◽  
Author(s):  
Chantelle L. Ferland ◽  
Erin P. Harris ◽  
Mai Lam ◽  
Laura A. Schrader

Evidence suggests that when presented with novel acute stress, animals previously exposed to chronic homotypic or heterotypic stressors exhibit normal or enhanced hypothalamic-pituitary-adrenal (HPA) response compared with animals exposed solely to that acute stressor. The molecular mechanisms involved in this effect remain unknown. The extracellular signal-regulated kinase (ERK) is one of the key pathways regulated in the hippocampus in both acute and chronic stress. The aim of this study was to examine the interaction of prior chronic stress, using the chronic variable stress model (CVS), with exposure to a novel acute stressor (2,5-dihydro-2,4,5-trimethyl thiazoline; TMT) on ERK activation, expression of the downstream protein BCL-2, and the glucocorticoid receptor co-chaperone BAG-1 in control and chronically stressed male rats. TMT exposure after chronic stress resulted in a significant interaction of chronic and acute stress in all 3 hippocampus subregions on ERK activation and BCL-2 expression. Significantly, acute stress increased ERK activation, BCL-2 and BAG-1 protein expression in the dentate gyrus (DG) of CVS-treated rats compared with control, CVS-treated alone, and TMT-only animals. Furthermore, CVS significantly increased ERK activation in medial prefrontal cortex, but acute stress had no significant effect. Inhibition of corticosterone synthesis with metyrapone had no significant effect on ERK activation in the hippocampus; therefore, glucocorticoids alone do not mediate the molecular effects. Finally, because post-translational modifications of histones are believed to play an important role in the stress response, we examined changes in histone acetylation. We found that, in general, chronic stress decreased K12H4 acetylation, whereas acute stress increased acetylation. These results indicate a molecular mechanism by which chronic stress-induced HPA axis plasticity can lead to neurochemical alterations in the hippocampus that influence reactivity to subsequent stress exposure. This may represent an important site of dysfunction that contributes to stress-induced pathology such as depression, anxiety disorders, and posttraumatic stress disorder.


2017 ◽  
Author(s):  
Romy Wichmann ◽  
Caitlin M. Vander Weele ◽  
Ariella S. Yosafat ◽  
Evelien H.S. Schut ◽  
Jeroen P. H. Verharen ◽  
...  

AbstractStress is a risk factor for many neuropsychiatric disorders, and the mesolimbic dopamine (DA) pathway is a crucial node of vulnerability. Despite the high prevalence of stress-related neuropsychiatric disorders in women, preclinical knowledge on the impact of stress on neural circuitry has predominantly been acquired in males. Here, we examine how a non-social stressor impacts the effect of DA neurotransmission on social and reward-related behaviors in female mice. Acute stress exposure attenuated the anti-social effects of photoinhibiting ventral tegmental area (VTA) DA neurons and transformed photoactivation of these cells into an anti-social signal. Fast-scan cyclic voltammetry (FSCV) revealed an enhancement in optogenetically-induced DA release after stress. 60 days after stress, mice showed distinct patterns of intra-cranial self-stimulation of VTA DA neurons. Our results reveal the impact stress exerts on females and show that neural and behavioral changes induced by acute stress exposure are still present months later.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katherine Knauft ◽  
Alexander Waldron ◽  
Mishali Mathur ◽  
Vrinda Kalia

AbstractExecutive functions are cognitive processes that facilitate goal-directed behavior by enabling us to direct and control our thoughts. Cognitive flexibility is an executive function characterized by the ability to mentally shift between rules, strategies, or tasks. Several studies have reported that acute (brief) stress impairs cognitive flexibility. Even though an individual’s perception of their chronic stress levels is shown to influence effects of future stressors, the interactive effect of acute and perceived chronic stress on cognitive flexibility is not known. We conducted two experiments to address this gap. In both studies, perceived chronic stress was measured using the Perceived Stress Scale. Acute stress was induced using the Cold Pressor Test. Number of perseverative errors on the Wisconsin Card Sorting Test was used as an indicator of cognitive flexibility. In Study 2, we also measured salivary alpha amylase as a marker of the physiological stress response. Data from our two studies are consistent with the hypothesis that an individual’s perception of their chronic stress level may impact the effect of acute stress on perseveration. In Study 1, we observed a significant interaction between acute and perceived chronic stress on perseverative errors, such that only individuals who reported high levels of perceived chronic stress prior to acute stress exposure showed no change in perseveration following the acute stress manipulation. This effect did not differ based on participant sex. In Study 2, we found a similar interaction effect of acute and perceived chronic stress on perseverative errors in an all-woman sample. After identifying salivary alpha amylase responders and non-responders, we observed a strong, negative correlation between perceived chronic stress and perseverative errors amongst the responders only. Our data highlight the value in studying salivary alpha amylase in response to acute stress exposure. Additionally, perceived chronic stress emerged as a key variable in the relationship between acute stress and cognitive flexibility. Overall, our work suggests that future research interested in interrogating moderators in the relationship between acute stress and cognition would benefit from inclusion of measures of chronic stress.


Author(s):  
Corey Fee ◽  
Thomas Prevot ◽  
Keith Misquitta ◽  
Mounira Banasr ◽  
Etienne Sibille

AbstractAltered activity of corticolimbic brain regions is a hallmark of stress-related illnesses, including mood disorders, neurodegenerative diseases, and substance abuse disorders. Acute stress adaptively recruits brain region-specific functions for coping, while sustained activation under chronic stress may overwhelm feedback mechanisms and lead to pathological cellular and behavioral responses. The neural mechanisms underlying dysregulated stress response and how they contribute to behavioral deficits are poorly characterized. Here, we tested whether prior exposure to chronic restraint stress (CRS) or unpredictable chronic mild stress (UCMS) in mice could alter neuronal response to acute stress and whether these changes are associated with chronic stress-induced behavioral deficits. More specifically, we assessed neuronal activation indexed by c-Fos+ cell counts in 24 stress- and mood-related brain regions, and determined if changes in acute stress-induced neuronal activation were linked to chronic stress-induced behavioral impairments. Results indicated that CRS and UCMS led to convergent physiological and anxiety-like deficits, whereas cognition was impaired only in UCMS mice. CRS and UCMS exposure exacerbated neuronal activation in response to an acute stressor in anterior cingulate cortex (ACC) area 24b and ventral hippocampal (vHPC) CA1, CA3, and subiculum. In dysregulated brain regions, levels of neuronal activation were positively correlated with principal components capturing variance across widespread behavioral alterations relevant to stress-related disorders. Our data supports an association between a dysregulated stress response, altered corticolimbic excitation/inhibition balance, and the expression of maladaptive behaviors.HighlightsChronic stress models produce variable profiles of physiological deficits, anxiety-like behavior, and impaired cognitionAcute stress-induced activation of ACC A24b & vHPC is exacerbated by prior chronic stress exposureIn regions dysregulated by chronic stress, altered neuronal activation is positively correlated with behavioral deficits


2021 ◽  
Vol 12 ◽  
Author(s):  
Allan Kalungi ◽  
Jacqueline S. Womersley ◽  
Eugene Kinyanda ◽  
Moses L. Joloba ◽  
Wilber Ssembajjwe ◽  
...  

Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2.Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs.Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5–17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs.Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs.Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs.


Stresses ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 16-29
Author(s):  
Christine Fahrngruber-Velasquez ◽  
Kalina Duszka ◽  
Jürgen König

Stress, mood, and eating behavior play an important role in appetite and weight regulation. In particular, ghrelin, as the only known orexigenic hormone, has been suggested to be an influential mediator in food intake responses to stress. The exact role of ghrelin in the hypothalamic–pituitary–adrenal axis is still unknown and further challenged by the psychological aspects of stress and eating behavior. This study aimed to assess the effect of chronic stress and subjective concern about eating on acute stress-induced changes in acylated ghrelin. In a 2-day study, sixteen healthy male participants were confronted with a stressful situation as well as a control situation. Additional measurements of heart rate, subjective hunger ratings, and subjective mood ratings were made to assess successful acute stress induction. The linear mixed model approach revealed a significant effect of acute stress on acylated ghrelin for a study-day*chronic-stress interaction (p < 0.001). Concern about eating did not affect acylated ghrelin levels after acute stress exposure. The significant interaction showed that lower chronic stress exposure was associated with a stronger acylated ghrelin response after acute stress exposure versus control condition. At the same time, participants with higher chronic stress exposure showed a blunted acylated ghrelin response after acute stress exposure compared to the control situation. Our findings indicate that chronic stress exposure can influence acylated ghrelin response after acute stress encounters, possibly affecting subsequent food intake and explaining the often diverse outcome in measurements of acute stress responses.


2018 ◽  
Author(s):  
Franziska Lautenbach

BACKGROUND Dealing with stress is of central importance. Lately, smartphone applications (apps) are deployed in stress interventions as they offer maximal flexibility for users. First results of experimental studies show that anti-stress apps effect subjective perception of stress positively (Ly et al., 2014). However, current literature lacks studies on physiological stress reactions (e.g., cortisol), although they are of special interest to health issues. OBJECTIVE Therefore, the aim of this study was to investigate the effectiveness of an anti-stress app in chronic and acute stress reduction on a physiological (cortisol) and psychological level (subjective perception of stress) in comparison to a face-to-face and a control group in a pre-post design, for the first time. METHODS Sixty-two participants took part in the pretesting procedure (drop-out of 53 %). Based on age, gender, physical activity and subjectively perceived acute stress due to the Trier Social Stress Test for groups (TSST-G; von Dawans et al., 2011) as well as based on subjectively chronic stress assessed during the pretest, participants were parallelized in three groups (anti-stress-app: n = 10, face-to-face: n = 11, control group: n = 9). RESULTS After six weeks of the cognitive-based resource-oriented intervention, participants were exposed to the TSST-G for post testing. Results did not show a change of cortisol secretion or cognitive appraisal of the acute stressor. Further, no changes were detected in the chronic physiological stress reaction. CONCLUSIONS Possible causes are discussed extensively. CLINICALTRIAL no


Sign in / Sign up

Export Citation Format

Share Document