Skip to main content
Download PDF

Behavioral and metabolic effects of escapable electric foot shock stress in male mice

BMC Research Notes volume 18, Article number: 127 (2025) Cite this article

Abstract

Background

The pathophysiology of post-traumatic stress disorder (PTSD) is not fully understood, prompting research using animal models. One of the approaches to induce PTSD-like traits in rodents involves exposure to unavoidable, unpredictable electric foot shocks. This study explored the effects of repeated electric foot shocks on behavior, hematology, and metabolic parameters in male C57BL/6J mice. The mice were subjected to 15 electrical stimuli (each 0.8 mA for 10 s, 10 s interval between sessions) in an electric foot shock apparatus featuring metal floor bars and two insulating bars for two consecutive days.

Results

Stressed mice showed enhanced memory retention of fear, as evidenced by an increased number of freezing events in the aversive context test. In the elevated plus maze test, stressed mice spent significantly less time in the open arms, indicating anxious behavior. However, no significant behavioral differences were observed between the stressed and control groups in the open field test. Stressed mice had a larger hypothalamic mass, elevated liver lipid peroxide levels, and a higher red blood cell count, with no changes in total leukocyte count. Thus, escapable foot shock induces fear response, anxiety-like behavior and minor metabolic changes in mice.

Peer Review reports

Introduction

Post-traumatic stress disorder (PTSD) is a complex psychiatric condition that can develop after exposure to a traumatic event [1]. For a better understanding of the molecular mechanisms of PTSD in humans, several animal models of PTSD have been developed in recent years. In rodents, PTSD-induced trauma may be caused by physical, social, or psychological stressors [2, 3]. Electric foot shock is the most widely used traumatic factor in rodent studies of anxiety and PTSD [4,5,6].

The consideration of PTSD as a highly heterogeneous disorder makes modeling PTSD in small animals significantly challenging [7]. In the electric foot shock model, the exposure to uncontrollable and unpredictable stressors mimics the traumatic experience, which can lead to alterations in neurobiological pathways involved in fear and stress responses, such as changes in the hypothalamic-pituitary-adrenal (HPA) axis, amygdala hyperactivity, and impaired synaptic plasticity [8, 9]. The electric foot shock model has shown that certain pharmacological and behavioral interventions that are effective in humans can also mitigate PTSD-like symptoms in mice [10] indicating the predictive validity of the mouse model.

In most studies of PTSD in mice, inescapable and unpredictable electric foot shocks are used to model PTSD symptoms effectively [3]. Unavoidable stress paradigm, such as inescapable electric foot shock reflects PTSD symptoms observed in humans, including hyperarousal, impaired fear extinction, and heightened anxiety [3]. However, unavoidable stress models do not fully capture the spectrum of human trauma responses, particularly resilience and adaptive coping mechanisms. Escapable shock paradigms, where animals can terminate the stressor, are less common in PTSD research but are occasionally used to study resilience mechanisms and potential interventions to improve coping strategies. We aimed to test whether mice develop PTSD-like symptoms if they are able to avoid stressors and thus have a feeling of conditional safety. In addition, the study assessed the effects of foot-escapable electric shock-induced stress on hematological and biochemical parameters in mice.

Methods

Animals, experimental design and behavioral tests

Two-three-month-old male C57BL/6J mice were randomly divided into control and experimental groups (see details in Supplementary materials). Experimental mice were placed in a chamber with two walls and a lid made of transparent plexiglass, and two walls made of white plexiglass with a metal mesh floor, connected to a stimulus generator. We also placed two insulating bars across the metal floor bars in the cage. This was done to allow the mice to avoid some of the electric foot shocks (Fig. 1A). On days 0 and 1 mice were subjected to 15 electric stimuli (intensity 0.8 mA; duration 10 s; interval between sessions 10 s) for 8 min in total [3]. Electric foot shock was combined with contextual trauma reminder through re-exposure to shock chambers, so-called the aversive context procedure. For this, on days 2 and 7 after exposure to the electric stimulus, the mice were placed in a shock chamber for 8 min but without administering electric foot shocks. Freezing was defined as the absence of movement, except for breathing, for at least 3 s. The control group of mice was placed in the chamber without electric foot shocks on days 0, 1, 2 and 7 for 8 min. On day 9 of the experiment, an open-field test [11, 12] was performed, and on day 11, an elevated plus maze test [13] was conducted for males of both control and experimental groups. On day 14, animals were euthanized using light carbon dioxide anesthesia in a chamber followed by blood collection and manual cervical dislocation [14].

Fig. 1
figure 1

Experimental design and behavioral tests. (A) Male C57BL/6J mice were randomly divided into two groups: control (n = 7 mice) and experimental (n = 7 mice). Mice from the experimental group were subjected to the foot shock procedure as described in the Materials and Methods. The aversive context test was performed twice: the day after the stress procedure (day 2) and seven days after stress exposure (day 7). The open field test was conducted on day 9 of the experiment. The elevated plus maze test (EPM) was performed on day 11 of the experiment. (B) Number of freezing events in the aversive context on day 2 after stress exposure, (C) number of freezing events in the aversive context on day 1 after stress exposure, (D) time spent in the open arms of the elevated plus maze, (E) average speed of mice in the open field, (F) time spent in the central squares of the open field, and (G) number of fecal boli per mice in the open field. Data are presented as mean ± SEM, n = 6–7. Significant differences (*p < 0.05) between the control and experimental groups were determined using an unpaired Student’s t-test

Full size image

Hematological parameters

Blood was collected by puncturing the right retro-orbital sinus and divided into two portions. The first portion was used to obtain plasma, and the second portion was used immediately for hematologic studies. After euthanasia and blood sampling, mice were decapitated, and the cortex was sampled.

The concentration of total hemoglobin (Hb), levels of hematocrit, and total number of erythrocytes and leukocytes were determined as described above [15] (details in Supplementary material).

Determination of metabolite levels and activities of PON and MPO in blood plasma

The concentrations of total cholesterol, triacylglycerides, glucose and glycogen were determined by using diagnostic kits from Felicit-Diagnostics (Ukraine) according to the manufacturer’s instructions [16]. Paraoxonase (PON) and myeloperoxidase (MPO) activities were measured as described previously [17, 18].

Spectrophotometric assays of lipid peroxides and carbonyl groups in proteins

Lipid peroxides (LOOH) were determined by ferrous oxidation/xylenol orange assay [19]. Quantification of carbonyl groups in proteins was performed by their reaction with 2,4-dinitrophenylhydrazine [19]. Protein concentration was determined by the Bradford assay [20].

Statistical analysis

Statistical analysis and visualization were performed using GraphPad Prism (version 10.0.0 for Windows). Data were analyzed by unpaired Student’s t-test with p < 0.05 as statistically different. The chosen sample size was based on power analysis calculations (https://wnarifin.github.io/ssc/ssanimal.html) and function pwr.t.test in R package “pwr” (with effect size 1.75, implying a strong effect, and power 0.8).

Results

Behavioral tests

In the aversive context test, the number of freezing episodes was recorded. On the second day after stress exposure, stressed mice exhibited a significantly higher number of freezing events compared with the control group, showing a 24.6-fold increase (p = 0.0001) (Fig. 1B). However, by day 7, this difference between control and experimental mice was no longer significant, with only a trend observed (p = 0.06) (Fig. 1C). In the elevated maze, stressed mice spent 88% less time in the open arms than the control group (p = 0.0004) (Fig. 1D). In the open field test, stressed mice showed no significant differences in movement speed, time spent in the central zone, or defecation count; however, a trend toward increased time spent in the inner quadrants was observed (Fig. 1E-F).

Mass of organs

We found a higher mass of the hypothalamus, by 29%, in the mice subjected to electric foot shocks (p = 0.019) but the total brain mass was not affected by stress exposure (Table 1). There were no differences in the mass of the liver, spleen, heart, cortex, intermediate brain, and olfactory bulbs between groups (Table 1).

Table 1 Organ mass in control mice and mice subjected to electric foot shock
Full size table

Hematology and blood plasma biochemistry

Hematocrit, hemoglobin level, and total leukocyte count were unaffected (Fig. 2A, B, D). There was a 37% increase in the number of erythrocytes in mice exposed to electric foot shock (p = 0.01) (Fig. 2C). No differences were in the content of glucose, total protein, total cholesterol, and interleukin 1-β (Fig. 2E-G, J) as well as in the activities of myeloperoxidase and paraoxonase (Fig. 2H, I) between groups.

Fig. 2
figure 2

Blood plasma parameters in control mice and mice subjected to electric foot shock. (A) Hematocrit, (B) hemoglobin, (C) erythrocyte count, (D) leukocyte count, (E) glucose, (F) total protein, (G) total cholesterol, (H) myeloperoxidase (MPO) activity, (I) paraoxonase (PON) activity, and (J) interleukin 1β level. Data are presented as mean ± SEM, n = 6–7. Significant differences (*p < 0.05) between the control and experimental groups were determined using an unpaired Student’s t-test

Full size image

Biochemical parameters in organs

The levels of glycogen in the cortex and liver and levels of TAG and carbonyl proteins in the liver were unaffected by stress exposure (Fig. 3A-C, B). The content of lipid peroxides in the cortex and intermediate brain of stressed mice did not differ from the control values (Fig. 3E, F). However, we observed 46% higher lipid peroxide levels in the liver of stressed mice (p = 0.0195) (Fig. 3G).

Fig. 3
figure 3

Biochemical parameters in the organs of control mice and mice subjected to electric foot shock. Glycogen levels in the cortex (A) and liver (B), triacylglyceride levels in the liver (C), levels of protein carbonyls in the liver (D), lipid peroxides in the cortex (E), diencephalon (F), and liver (G). Data are presented as mean ± SEM, n = 6–7. Significant differences (*p < 0.05) between the control and experimental groups were determined using an unpaired Student’s t-test

Full size image

Discussion

Our results show that escapable electrical stress causes anxiety symptoms but minor metabolic changes. The enhanced freezing events observed in the stressed group suggest that they formed a strong fear association with the context in which mice experienced the foot electrical foot shock, which is comparable to the intrusive memories of trauma seen in PTSD patients [21]. However, the absence of significant differences at day 7 indicates a potential reduction in fear response or adaptation over time. This pattern is consistent with previous studies indicating that fear memories may weaken over time or that animals may habituate to the experimental context [22]. Within-group variation in the number of freezing events reflects the complexity of trauma memory and its impact on behavior, highlighting the individual differences in trauma processing and memory. Individual variability in stress responses may be caused by the complex interplay of genetic, environmental, and neurobiological factors. It was previously shown that adaptive and non-adaptive anxiety phenotypes may differ within mice cohorts [23].

Our data confirm the hypothesis that exposure to traumatic stressors leads to anxiety and reduced exploratory behavior [24]. Acute stress is known to activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to anxiety and risk-aversion behaviors [25]. The increased mass of the hypothalamus in stressed mice may reflect neuroplastic changes or enhanced activity in this stress-regulating brain region. Additionally, hypothalamic growth may indicate adaptive responses to stress, possibly involving increased synaptic connections or cellular hypertrophy [26]. The preference for the inner zone of stressed mice in the OF test might be due to associative learning. The visual cue of the white walls associated with the stressor (electric foot shock) could have conditioned the mice to prefer certain areas, illustrating the role of context in fear memory [27]. However, the lack of significant changes in locomotor activity or defecation in the OF test is in line with previous studies which have shown that stress-induced behavioral and physiological changes were not associated with motor impairment [28, 29].

The increase in erythrocyte count in stressed mice may reflect a physiological response to increased metabolic demands or stress-induced erythropoiesis [30]. Compensatory response to stress potentially is driven by elevated erythropoietin activity or increased oxygen demand [31]. Indeed, stress often results in the activation of the sympathetic nervous system and the release of catecholamines, which can stimulate erythropoiesis through the erythropoietin pathway [32]. However, unchanged hematocrit levels and hemoglobin levels may be connected with variations in erythrocyte cell size [33].

Any stress exposure is thought to increase the production of reactive oxygen species followed by an increasing the damages of lipids, proteins, and DNA [34,35,36]. Previously, it was found that electric foot stress caused oxidative stress development in the brain of rodents depending on stress intensity [37, 38]. We did not observe changes in lipid peroxide levels, which are intermediate products of lipid oxidation, in different parts of the brain of mice exposed to stress. This may be due to the fact that the mice were able to avoid exposure to electric foot shock by choosing isolated rods and therefore not be damaged, but rather to develop adaptive resistance. The absence of significant changes in hematological parameters and pro-inflammatory blood markers, MPO and IL-1β, may also indicate resilience to stress. Elevated levels of lipid peroxides in the liver indicate increased oxidative stress in this organ, which may be a consequence of direct exposure to electric foot shock due to disrupted mitochondrial function [39].

Most studies commonly used an inescapable model of stress [40,41,42]. However, a few studies have aimed to test the effects of predictability on escape learning associated with escapable stress [43,44,45]. For example, rats subjected to tail electro-shock that can be terminated by operant turning of a wheel, and testing for escaping electro-shock by operant running in a two-way shuttle box [43]. Mice exposed to uncontrollable stressors (e.g., unavoidable shocks) showed greater physiological and psychological distress than those exposed to controllable stressors [44, 45]. A previous study compared the effect of escapable and inescapable shock freezing and showed a common number of freezing events as a behavioral index of fear [45]. Thus, the perception of control plays a significant role in how stress is experienced and how it impacts overall health. The controllable stress component of the paradigm includes operant conditioning to learn the escape response [45]. Indeed, under stress exposure in our conditions, mice exhibited high levels of escape behavior. The serotonergic (5-HTergic) system is involved in the regulation of mood and anxiety [46]. Uncontrollable stress activates 5-HT neurons more as compared to controllable stress [43].

Conclusions

This study demonstrates that escapable moderate foot shock induces anxiety-like behavior and fear response in male mice. Stress exposure increased hypothalamic mass, liver lipid peroxides, and erythrocyte count, which may correlate with behavioral changes, such as altered anxiety-like behavior and heightened arousal in the elevated plus maze (Fig. 4). Metabolic changes reflected stress-induced hypothalamic adaptation, oxidative stress modulation in the liver, and altered hematopoiesis. The previous finding suggests that changes in blood oxygen-carrying capacity can impact cognitive performance and emotional regulation [47]. In general, when mice are exposed to electric foot shock and have the opportunity to avoid it with repeated exposure, they apparently take advantage of this opportunity. Herewith, our experimental design shows that even when mice are able to avoid repeated traumatic stress, they develop fear of the stress itself and develop anxiety symptoms. Obviously, the perception of control, activation of the HPA axis, and metabolic changes in various organs play a key role in shaping the effects of stress that can be overcome.

Fig. 4
figure 4

Schematic summarizing the stress-induced biochemical changes with behavioral manifestation. Exposure to extreme stress in the form of escapable electric foot shock leads to activation of the HPA axis in the brain and contributes to the development of hypothalamic hypertrophy after traumatic stress exposure. Activated HPA axis leads to glucocorticoid release, which, in turn, may contribute to erythropoiesis. A higher erythrocyte count results in oxidative stress and increased lipid peroxide levels that was observed in our study. Oxidative stress-induced changes alter the functioning of the amygdala and hippocampus which contribute to fear-associated memory and anxiety behavior

Full size image

Discussion of limitations

The key limitation of our study is the relatively small sample size of mice, which may limit the statistical power and generalizability of the findings. A larger sample size would provide more robust conclusions and help account for individual variability. We generated a generalized scheme that demonstrates the potential relationship between the observed effects of biochemical parameters (marked by red font) and behavioral manifestations (Fig. 4). The proposed summary figure includes stages that have not been established by our data and require further validation through additional experiments (marked by black font). We observed an increase in hypothalamic mass in stressed mice; however, we did not perform histological or molecular analyses to confirm structural changes. Future studies using immunohistochemistry for neuronal markers, as well as molecular assessments of neuroplasticity-related factors (e.g., BDNF), would provide more insight into stress-induced neuroplasticity.

Stress-induced increases in erythrocyte count should be validated using flow cytometry. Measuring erythropoietin levels would help determine whether the observed hematological changes result from increased erythropoiesis or altered red blood cell turnover.

Data availability

The data reported in this study is available from the corresponding authors upon request.

Abbreviations

PTSD:

Post-traumatic stress disorder

PON:

Paraoxonase

MPO:

Myeloperoxidase

HPA:

Axis Hypothalamic-pituitary-adrenal axis

LOOH:

Lipid peroxides

TAG:

Triacylglycerides

References

  1. Jones K, Boschen M, Devilly G, Vogler J, Flowers H, Winkleman C, Wullschleger M. Risk and protective factors that predict posttraumatic stress disorder after traumatic injury: A systematic review. Health Sci Rev. 2024;10:100147.

    Google Scholar 

  2. Borghans B, Homberg JR. Animal models for posttraumatic stress disorder: an overview of what is used in research. World J Psychiatry. 2015;5(4):387–96.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Verbitsky A, Dopfel D, Zhang N. Rodent models of post-traumatic stress disorder: behavioral assessment. Transl Psychiatry. 2020;10(1):132.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Masterson FA. Suppression of the rat’s locomotor activity at low intensities of electric foot shock. Behav Res Methods Instrum. 1981;13:31–6.

    Article  Google Scholar 

  5. Pissiota A, Frans O, Fernandez M, von Knorring L, Fischer H, Fredrikson M. Neurofunctional correlates of posttraumatic stress disorder: a PET symptom provocation study. Eur Arch Psychiatry Clin Neurosci. 2002;252(2):68–75.

    Article  PubMed  Google Scholar 

  6. Clausen AN, Francisco AJ, Thelen J, Bruce J, Martin LE, McDowd J, et al. PTSD and cognitive symptoms relate to inhibition-related prefrontal activation and functional connectivity. Depress Anxiety. 2017;34(5):427–36.

    Article  CAS  PubMed  Google Scholar 

  7. Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The posttraumatic stress disorder checklist for DSM-5 (PCL-5): development and initial psychometric evaluation. J Trauma Stress. 2015;28(6):489–98.

    Article  PubMed  Google Scholar 

  8. Goswami S, Rodríguez-Sierra O, Cascardi M, Paré D. Animal models of post-traumatic stress disorder: face validity. Front Neurosci. 2013;7:89.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sherin JE, Nemeroff CB. Post-traumatic stress disorder: the Neurobiological impact of psychological trauma. Dialogues Clin Neurosci. 2011;13(3):263–78.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gasparyan A, Navarro D, Navarrete F, Manzanares J. Pharmacological strategies for post-traumatic stress disorder (PTSD): from animal to clinical studies. Neuropharmacology. 2022;218:109211.

    Article  CAS  PubMed  Google Scholar 

  11. Rodriguez A, Zhang H, Klaminder J, Brodin T, Andersson PL, Andersson M. ToxTrac: A fast and robust software for tracking organisms. Meth Ecol Evol. 2018;9:460–4.

    Article  Google Scholar 

  12. Seibenhener ML, Wooten MC. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp. 2015;96:e52434.

    Google Scholar 

  13. Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007;2(2):322–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bayliak MM, Vatashchuk MV, Gospodaryov DV, Hurza VV, Demianchuk OI, Ivanochko MV, et al. High fat high fructose diet induces mild oxidative stress and reorganizes intermediary metabolism in male mouse liver: Alpha-ketoglutarate effects. Biochim Biophys Acta Gen Subj. 2022;1866(12):130226.

    Article  CAS  PubMed  Google Scholar 

  15. Sorochynska OM, Bayliak MM, Gospodaryov DV, Vasylyk YV, Kuzniak OV, Pankiv TM, et al. Every-other-day feeding decreases glycolytic and mitochondrial energy-producing potentials in the brain and liver of young mice. Front Physiol. 2019;10:1432.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Semaniuk UV, Gospodaryov DV, Strilbytska OM, Kucharska AZ, Sokół-Łętowska A, Burdyliuk NI, et al. Chili pepper extends lifespan in a concentration-dependent manner and confers cold resistance on Drosophila melanogaster cohorts by influencing specific metabolic pathways. Food Funct. 2022;13(15):8313–28.

    Article  CAS  PubMed  Google Scholar 

  17. Vatashchuk M, Hurza V, Bayliak M. Adapting of spectrophotometric assay of paraoxonase activity with 4-Nitrophenylacetate for murine plasma and liver. J Vasyl Stefanyk Precarpath Nat Univers. 2022;9(4):6–14.

    Article  Google Scholar 

  18. Yadav MK, Pradhan PK, Sood N, Chaudhary DK, Verma DK, Debnath C, et al. Innate immune response of Indian major carp, Labeo Rohita infected with oomycete pathogen aphanomyces invadans. Fish Shellfish Immunol. 2014;39(2):524–31.

    Article  CAS  PubMed  Google Scholar 

  19. Lushchak V, Semchyshyn H, Lushchak O, Mandryk S. Diethyldithiocarbamate inhibits in vivo Cu,Zn-superoxide dismutase and perturbs free radical processes in the yeast Saccharomyces cerevisiae cells. Biochem Biophys Res Commun. 2005;338(4):1739–44.

    Article  CAS  PubMed  Google Scholar 

  20. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1):248–54.

    Article  CAS  PubMed  Google Scholar 

  21. Iyadurai L, Visser RM, Lau-Zhu A, Porcheret K, Horsch A, Holmes EA, James EL. Intrusive memories of trauma: A target for research bridging cognitive science and its clinical application. Clin Psychol Rev. 2019;69:67–82.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Alemany-González M, Wokke ME, Chiba T, Narumi T, Kaneko N, Yokoyama H, et al. Fear in action: fear conditioning and alleviation through body movements. iScience. 2024;27(3):109099.

    Article  PubMed  PubMed Central  Google Scholar 

  23. van der Goot MH, Keijsper M, Baars A, Drost L, Hendriks J, Kirchhoff S, et al. Inter-individual variability in habituation of anxiety-related responses within three mouse inbred strains. Physiol Behav. 2021;239:113503.

    Article  PubMed  Google Scholar 

  24. Sturman O, von Ziegler L, Privitera M, Waag R, Duss S, Vermeiren Y, et al. Chronic adolescent stress increases exploratory behavior but does not appear to change the acute stress response in adult male C57BL/6 mice. Neurobiol Stress. 2021;15:100388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Belo-Silva AE, de Gusmão Taveiros Silva NK, Marianno P, de Araújo Costa G, da Rovare VP, Bailey A, et al. Effects of the combination of chronic unpredictable stress and environmental enrichment on anxiety-like behavior assessed using the elevated plus maze in Swiss male mice: Hypothalamus-pituitary-adrenal axis-mediated mechanisms. Horm Behav. 2024;162:105538.

    Article  PubMed  Google Scholar 

  26. Herman JP, Flak J, Jankord R. Chronic stress plasticity in the hypothalamic paraventricular nucleus. Prog Brain Res. 2008;170:353–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liberzon I, Abelson JL. Context processing and the neurobiology of post-traumatic stress disorder. Neuron. 2016;92(1):14–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pynoos RS, Ritzmann RF, Steinberg AM, Goenjian A, Prisecaru I. A behavioral animal model of posttraumatic stress disorder featuring repeated exposure to situational reminders. Biol Psychiatry. 1996;39(2):129–34.

    Article  CAS  PubMed  Google Scholar 

  29. Zhang LM, Yao JZ, Li Y, Li K, Chen HX, Zhang YZ, Li YF. Anxiolytic effects of flavonoids in animal models of posttraumatic stress disorder. Evid Based Complement Alternat Med. 2012;2012:623753.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ruan B, Paulson RF. Metabolic regulation of stress erythropoiesis, outstanding questions, and possible paradigms. Front Physiol. 2023;13:1063294.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhang Y, Wang L, Dey S, Alnaeeli M, Suresh S, Rogers H, Teng R, Noguchi CT. Erythropoietin action in stress response, tissue maintenance and metabolism. Int J Mol Sci. 2014;15(6):10296–333.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Munley JA, Kelly LS, Mohr AM. Adrenergic modulation of erythropoiesis after trauma. Front Physiol. 2022;13:859103.

    Article  PubMed  PubMed Central  Google Scholar 

  33. O’Connell KE, Mikkola AM, Stepanek AM, Vernet A, Hall CD, Sun CC, et al. Practical murine hematopathology: a comparative review and implications for research. Comp Med. 2015;65(2):96–113.

    PubMed  PubMed Central  Google Scholar 

  34. de Munter J, Pavlov D, Gorlova A, Sicker M, Proshin A, Kalueff AV, et al. Increased oxidative stress in the prefrontal cortex as a shared feature of depressive- and PTSD-Like syndromes: effects of a standardized herbal antioxidant. Front Nutr. 2021;8:661455.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Garaschuk O, Semchyshyn HM, Lushchak VI. Healthy brain aging: interplay between reactive species, inflammation and energy supply. Ageing Res Rev. 2018;43:26–45.

    Article  CAS  PubMed  Google Scholar 

  36. Lushchak VI, Duszenko M, Gospodaryov DV, Garaschuk O. Oxidative stress and energy metabolism in the brain: midlife as a turning point. Antioxid (Basel). 2021;10(11):1715.

    Article  CAS  Google Scholar 

  37. Gönenç S, Açikgöz O, Kayatekin BM, Uysal N, Akhisaroglu M. Effects of footshock stress on superoxide dismutase and glutathione peroxidase enzyme activities and thiobarbituric acid reactive substances levels in the rat prefrontal cortex and striatum. Neurosci Lett. 2000;289(2):107–10.

    Article  PubMed  Google Scholar 

  38. Nisar R, Batool Z, Haider S. Electric foot-shock induces neurobehavioral aberrations due to imbalance in oxidative status, stress hormone, neurochemical profile, and irregular cortical-beta wave pattern in rats: A validated animal model of anxiety. Life Sci. 2023;323:121707.

    Article  CAS  PubMed  Google Scholar 

  39. Angelova PR, Esteras N, Abramov AY. Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: finding ways for prevention. Med Res Rev. 2021;41(2):770–84.

    Article  CAS  PubMed  Google Scholar 

  40. Sidles SJ, Kelly RR, Kelly KD, Hathaway-Schrader JD, Khoo SK, Jones JA, Cray JJ, LaRue AC. Inescapable foot shock induces a PTSD-like phenotype and negatively impacts adult murine bone. Dis Model Mech. 2024;17(1):dmm050044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Silva AI, Holanda VAD, Azevedo Neto JG, Silva Junior ED, Soares-Rachetti VP, Calo G, Ruzza C, Gavioli EC. Blockade of NOP receptor modulates anxiety-related behaviors in mice exposed to inescapable stress. Psychopharmacology. 2020;237(6):1633–42.

    Article  CAS  PubMed  Google Scholar 

  42. Van Dijken HH, Van der Heyden JA, Mos J, Tilders FJ. Inescapable footshocks induce progressive and long-lasting behavioural changes in male rats. Physiol Behav. 1992;51(4):787–94.

    Article  PubMed  Google Scholar 

  43. Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal Raphe nucleus. Nat Neurosci. 2005;8(3):365–71.

    Article  CAS  PubMed  Google Scholar 

  44. Machida M, Yang L, Wellman LL, Sanford LD. Effects of stressor predictability on escape learning and sleep in mice. Sleep. 2013;36(3):421–30.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Yang L, Wellman LL, Ambrozewicz MA, Sanford LD. Effects of stressor predictability and controllability on sleep, temperature, and fear behavior in mice. Sleep. 2011;34(6):759–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Araki R, Kita A, Ago Y, Yabe T. Chronic social defeat stress induces anxiety-like behaviors via downregulation of serotonin transporter in the prefrontal serotonergic system in mice. Neurochem Int. 2024;174:105682.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang Q, Haselden WD, Charpak S, Drew PJ. Could respiration-driven blood oxygen changes modulate neural activity? Pflugers Arch. 2023;475(1):37–48.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank our students V. Hurza, I. Labych, V. Derkachov, M. Ivanochko, N. Stefanyshyn, and M. Vatashchuk for technical assistance in collecting mouse tissues and measuring hematological parameters.

Funding

This work was supported by a grant from the Ministry of Education and Science of Ukraine [grant number 0123U101790].

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine

    Vitalii Balatskyi, Olha Strilbytska, Oleksandra Abrat, Anastasiia Tkachyk, Maria Lylyk, Volodymyr Lushchak & Maria Bayliak

Authors
  1. Vitalii Balatskyi
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Olha Strilbytska
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Oleksandra Abrat
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Anastasiia Tkachyk
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Maria Lylyk
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Volodymyr Lushchak
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Maria Bayliak
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

M.B. and V.L. developed the idea for the research and edited the manuscript. V.B., A.T., M.L., and O.A. performed all the experiments and collected the data. O.S. and V.B. analyzed and interpreted the data and were major contributors to the writing of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Volodymyr Lushchak or Maria Bayliak.

Ethics declarations

Ethics approval and consent to participate

All mouse protocols were approved by the Animal Experimental Committee of Vasyl Stefanyk Precarpathian National University (Ethics Review No: PNU-2023-M-012) and were conducted in accordance with the Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. The current study complies with the ARRIVE Guidelines for reporting in vivo experiments (https://arriveguidelines.org/arrive-guidelines).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Balatskyi, V., Strilbytska, O., Abrat, O. et al. Behavioral and metabolic effects of escapable electric foot shock stress in male mice. BMC Res Notes 18, 127 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13104-025-07189-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13104-025-07189-0

Keywords

BMC Research Notes

ISSN: 1756-0500

Contact us