Skip to main content

Advertisement

SpringerLink
Log in

Spontaneous recovery, time course, and circadian influence on habituation of the cardiovascular responses to repeated restraint stress in rats

  • Neuroscience
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

We investigated the spontaneous recovery, time course, and the influence of the time of day on the habituation of the cardiovascular responses with repeated exposure to restraint stress in male rats. Habituation of the corticosterone response to repeated restraint stress was also evaluated. The circulating corticosterone response decreased during both the stress and recovery periods of the tenth session of restraint. Habituation of the cardiovascular responses was identified as a faster return to baseline values of the heart rate (HR) and blood pressure (BP) during the recovery period of the tenth session of restraint. Habituation of the HR and BP was still observed after 10 days of discontinuation of the repeated exposure to restraint stress. However, spontaneous recovery of habituated responses was observed 20 days after the final restraint stress session. Time course analysis revealed decreased HR response during the recovery period of the third restraint session, without further reduction on the fifth, seventh, and tenth sessions. Decreased BP response was identified on the third and fifth sessions, whereas reduced tail skin temperature response was observed only on the fifth and seventh sessions. Regarding the time of day, habituation of the tachycardiac response was identified at the tenth session when repeated restraint stress was performed in the morning and night periods, but not in the afternoon. These findings provided evidence of spontaneous recovery of the habituation of cardiovascular responses to repeated restraint stress. Moreover, cardiovascular habituation was dependent on the number of trials and time of day.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Benini R, Oliveira LA, Gomes-de-Souza L, Crestani CC (2019) Habituation of the cardiovascular responses to restraint stress in male rats: influence of length, frequency and number of aversive sessions. Stress 22:151–161. https://doi.org/10.1080/10253890.2018.1532992

    Article  PubMed  Google Scholar 

  2. Benini R, Oliveira LA, Gomes-de-Souza L, Rodrigues B, Crestani CC (2020) Habituation of the cardiovascular responses to restraint stress is inhibited by exposure to other stressor stimuli and exercise training. J Exp Biol:jeb.219501. https://doi.org/10.1242/jeb.219501

  3. Bennett JM, Rohleder N, Sturmberg JP (2018) Biopsychosocial approach to understanding resilience: stress habituation and where to intervene. J Eval Clin Pract 24:1339–1346. https://doi.org/10.1111/jep.13052

    Article  PubMed  Google Scholar 

  4. Bhatnagar S, Huber R, Nowak N, Trotter P (2002) Lesions of the posterior paraventricular thalamus block habituation of hypothalamic-pituitary-adrenal responses to repeated restraint. J Neuroendocrinol 14:403–410. https://doi.org/10.1046/j.0007-1331.2002.00792.x

    Article  CAS  PubMed  Google Scholar 

  5. Blessing WW (2003) Lower brainstem pathways regulating sympathetically mediated changes in cutaneous blood flow. Cell Mol Neurobiol 23:527–538. https://doi.org/10.1023/A:1025020029037

    Article  CAS  PubMed  Google Scholar 

  6. Busnardo C, Crestani CC, Scopinho AA, Packard BA, Resstel LBM, Correa FMA, Herman JP (2019) Nitrergic neurotransmission in the paraventricular nucleus of the hypothalamus modulates autonomic, neuroendocrine and behavioral responses to acute restraint stress in rats. Prog Neuropsychopharmacol Biol Psychiatry 90:16–27. https://doi.org/10.1016/J.PNPBP.2018.11.001

    Article  CAS  PubMed  Google Scholar 

  7. Buynitsky T, Mostofsky DI (2009) Restraint stress in biobehavioral research: recent developments. Neurosci Biobehav Rev 33:1089–1098. https://doi.org/10.1016/j.neubiorev.2009.05.004

    Article  PubMed  Google Scholar 

  8. Cohen S, Vainer E, Matar MA, Kozlovsky N, Kaplan Z, Zohar J, Mathé AA, Cohen H (2015) Diurnal fluctuations in hpa and neuropeptide Y-ergic systems underlie differences in vulnerability to traumatic stress responses at different zeitgeber times. Neuropsychopharmacology 40:774–790. https://doi.org/10.1038/npp.2014.257

    Article  CAS  PubMed  Google Scholar 

  9. Crestani CC (2016) Emotional stress and cardiovascular complications in animal models: a review of the influence of stress type. Front Physiol 7:251. https://doi.org/10.3389/fphys.2016.00251

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cyr NE, Romero LM (2009) Identifying hormonal habituation in field studies of stress. Gen Comp Endocrinol 161:295–303. https://doi.org/10.1016/j.ygcen.2009.02.001

    Article  CAS  PubMed  Google Scholar 

  11. Danese A, McEwen BS (2012) Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav 106:29–39. https://doi.org/10.1016/j.physbeh.2011.08.019

    Article  CAS  PubMed  Google Scholar 

  12. Daut RA, Ravenel JR, Watkins LR, Maier SF, Fonken LK (2020) The behavioral and neurochemical effects of an inescapable stressor are time of day dependent. Stress 23:1–12. https://doi.org/10.1080/10253890.2019.1707180

    Article  CAS  Google Scholar 

  13. De Boer SF, Slangen JL, van der Gugten J (1988) Adaptation of plasma catecholamine and corticosterone responses to short-term repeated noise stress in rats. Physiol Behav. 44:273–280. https://doi.org/10.1016/0031-9384(88)90149-7

    Article  PubMed  Google Scholar 

  14. De Boer SF, Koopmans SJ, Slangen JL, Van Der Gugten J (1990) Plasma catecholamine, corticosterone and glucose responses to repeated stress in rats: effect of interstressor interval length. Physiol Behav 47:1117–1124. https://doi.org/10.1016/0031-9384(90)90361-7

    Article  PubMed  Google Scholar 

  15. Dhabhar FS (2019) The power of positive stress – a complementary commentary. Stress 22:526–529. https://doi.org/10.1080/10253890.2019.1634049

    Article  PubMed  Google Scholar 

  16. Dunn J, Scheving L, Millet P (1972) Circadian variation in stress-evoked increases in plasma corticosterone. Am J Physiol Content 223:402–406. https://doi.org/10.1152/ajplegacy.1972.223.2.402

    Article  CAS  Google Scholar 

  17. Fonken LK, Weber MD, Daut RA, Kitt MM, Frank MG, Watkins LR, Maier SF (2016) Stress-induced neuroinflammatory priming is time of day dependent. Psychoneuroendocrinology 66:82–90. https://doi.org/10.1016/j.psyneuen.2016.01.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gomez F, Houshyar H, Dallman MF (2002) Marked regulatory shifts in gonadal, adrenal, and metabolic system responses to repeated restraint stress occur within a 3-week period in pubertal male Rats. Endocrinology 143:2852–2862. https://doi.org/10.1210/endo.143.8.8929

    Article  CAS  PubMed  Google Scholar 

  19. Grissom N, Bhatnagar S (2009) Habituation to repeated stress: get used to it. Neurobiol Learn Mem 92:215–224. https://doi.org/10.1016/j.nlm.2008.07.001

    Article  PubMed  Google Scholar 

  20. Herman JP (2013) Neural control of chronic stress adaptation. Front Behav Neurosci 7. https://doi.org/10.3389/fnbeh.2013.00061

  21. Kant J, Mougey EH, Meyerhoff JL (1986) Diurnal variation in neuroendocrine response to stress in rats: plasma ACTH, β-Endorphin, β-LPH, corticosterone, prolactin and pituitary cyclic AMP responses. Neuroendocrinology 43:383–390. https://doi.org/10.1159/000124553

    Article  CAS  PubMed  Google Scholar 

  22. Keim KL, Sigg EB (1976) Physiological and biochemical concomitants of restraint stress in rats. Pharmacol Biochem Behav 4:289–297. https://doi.org/10.1016/0091-3057(76)90244-6

    Article  CAS  PubMed  Google Scholar 

  23. Koehl M, Bouyer JJ, Darnaudéry M, Le Moal M, Mayo W (2002) The effect of restraint stress on paradoxical sleep is influenced by the circadian cycle. Brain Res 937:45–50. https://doi.org/10.1016/S0006-8993(02)02463-0

    Article  CAS  PubMed  Google Scholar 

  24. Kräuchi K, Wirz-Justice A, Willener R, Campbell IC, Feer H (1983) Spontaneous hypertensive rats: behavioral and corticosterone response depend on circadian phase. Physiol Behav. 30:35–40. https://doi.org/10.1016/0031-9384(83)90035-5

    Article  PubMed  Google Scholar 

  25. Kusnecov AW, Shurin MR, Armfield A, Litz J, Wood P, Zhou D, Rabin BS (1995) Suppression of lymphocyte mitogenesis in different rat strains exposed to footshock during early diurnal and nocturnal time periods. Psychoneuroendocrinology 20:821–835. https://doi.org/10.1016/0306-4530(95)00009-7

    Article  CAS  PubMed  Google Scholar 

  26. Lachuer J, Delton I, Buda M, Tappaz M (1994) The habituation of brainstem catecholaminergic groups to chronically daily restraint stress is stress specific like that of the hypothalamo-pituitary-adrenal axis. Brain Res 638:196–202. https://doi.org/10.1016/0006-8993(94)90650-5

    Article  CAS  PubMed  Google Scholar 

  27. McCarty R (2016) Learning about stress: neural, endocrine and behavioral adaptations. Stress 19:449–475. https://doi.org/10.1080/10253890.2016.1192120

    Article  CAS  PubMed  Google Scholar 

  28. McEwen BS (1998) Protective and damaging effects of mediators. N Engl J Med 338:171–179. https://doi.org/10.1056/NEJM199801153380307

    Article  CAS  PubMed  Google Scholar 

  29. Miller DB (1988) Restraint-induced analgesia in the CD-1 mouse: interactions with morphine and time of day. Brain Res 473:327–335. https://doi.org/10.1016/0006-8993(88)90862-1

    Article  CAS  PubMed  Google Scholar 

  30. Nyhuis TJ, Sasse SK, Masini CV, Day HEW, Campeau S (2010) Lack of contextual modulation of habituated neuroendocrine responses to repeated audiogenic stress. Behav Neurosci 124:810–820. https://doi.org/10.1037/a0021203

    Article  PubMed  PubMed Central  Google Scholar 

  31. Pfister HP (1979) The glucocorticosterone response to novelty as a psychological stressor. Physiol Behav 23:649–652. https://doi.org/10.1016/0031-9384(79)90154-9

    Article  CAS  PubMed  Google Scholar 

  32. Rabasa C, Muñoz-Abellán C, Daviu N, Nadal R, Armario A (2011) Repeated exposure to immobilization or two different footshock intensities reveals differential adaptation of the hypothalamic-pituitary-adrenal axis. Physiol Behav 103:125–133. https://doi.org/10.1016/j.physbeh.2011.02.022

    Article  CAS  PubMed  Google Scholar 

  33. Rabasa C, Delgado-Morales R, Gomez-Roman A, Nadal R, Armario A (2013) Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water. Stress. 16:698–705. https://doi.org/10.3109/10253890.2013.824964

    Article  CAS  PubMed  Google Scholar 

  34. Rabasa C, Gagliano H, Pastor-Ciurana J, Fuentes S, Belda X, Nadal R, Armario A (2015) Adaptation of the hypothalamus-pituitary-adrenal axis to daily repeated stress does not follow the rules of habituation: a new perspective. Neurosci Biobehav Rev 56:35–49

    Article  CAS  PubMed  Google Scholar 

  35. Rankin CH, Abrams T, Barry RJ, Bhatnagar S, Clayton DF, Colombo J, Coppola G, Geyer MA, Glanzman DL, Marsland S, McSweeney FK, Wilson DA, Wu CF, Thompson RF (2009) Habituation revisited: An updated and revised description of the behavioral characteristics of habituation. Neurobiol Learn Mem 92:135–138. https://doi.org/10.1016/j.nlm.2008.09.012

    Article  PubMed  Google Scholar 

  36. Retana-Márquez S, Bonilla-Jaime H, Vázquez-Palacios G, Domínguez-Salazar E, Martínez-García R, Velázquez-Moctezuma J (2003) Body weight gain and diurnal differences of corticosterone changes in response to acute and chronic stress in rats. Psychoneuroendocrinology 28:207–227. https://doi.org/10.1016/S0306-4530(02)00017-3

    Article  PubMed  Google Scholar 

  37. Rybkin II, Zhou Y, Volaufova J, Smagin GN, Ryan DH, Harris RBS (1997) Effect of restraint stress on food intake and body weight is determined by time of day. Am J Physiol Integr Comp Physiol 273:R1612–R1622. https://doi.org/10.1152/ajpregu.1997.273.5.R1612

    Article  CAS  Google Scholar 

  38. Sterling P (2012) Allostasis: a model of predictive regulation. Physiol Behav 106:5–15. https://doi.org/10.1016/j.physbeh.2011.06.004

    Article  CAS  PubMed  Google Scholar 

  39. Tannenbaum B, Rowe W, Sharma S, Diorio J, Steverman A, Walker M, Meaney MJ (1997) Dynamic variations in plasma corticosteroid-binding globulin and basal HPA activity following acute stress in adult rats. J Neuroendocrinol 9:163–168. https://doi.org/10.1046/j.1365-2826.1997.t01-1-00550.x

    Article  CAS  PubMed  Google Scholar 

  40. Thompson RF (2009) Habituation: a history. Neurobiol Learn Mem 92:127–134. https://doi.org/10.1016/j.nlm.2008.07.011

    Article  PubMed  Google Scholar 

  41. Thompson RF, Spencer WA (1966) Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 73:16–43. https://doi.org/10.1037/h0022681

    Article  CAS  PubMed  Google Scholar 

  42. Torrellas A, Guaza C, Borrell J, Borrell S (1981) Adrenal hormones and brain catecholamines responses to morning and afternoon immobilization stress in rats. Physiol Behav 26:129–133. https://doi.org/10.1016/0031-9384(81)90088-3

    Article  CAS  PubMed  Google Scholar 

  43. Vodička M, Vavřínová A, Mikulecká A, Zicha J, Behuliak M (2020) Hyper-reactivity of HPA axis in Fischer 344 rats is associated with impaired cardiovascular and behavioral adaptation to repeated restraint stress. Stress:1–11. https://doi.org/10.1080/10253890.2020.1777971

Download references

Acknowledgments

The authors wish to thank Elisabete Z.P. Lepera and Rosana F.P. Silva for technical assistance.

Funding

This work was financially supported by CAPES/MEC/Brazilian government-Finance Code 001, as well as by grants from FAPESP (grant # 2015/05922-9 and 2017/19249-0), CNPq (grant # 456405/2014-3 and 431339/2018-0), and Scientific Support and Development Program of School of Pharmaceutical Sciences (UNESP). CCC (process # 305583/2015-8 and 304108/2018-9) is a CNPq research fellow.

Author information

Author notes

  1. Carlos E. Santos and Ricardo Benini contributed equally to this work.

Authors and Affiliations

  1. Department of Drugs and Pharmaceutics, Laboratory of Pharmacology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Rodovia Araraquara KM 01 (Campus Universitário), Araraquara, SP, 14800-903, Brazil

    Carlos E. Santos, Ricardo Benini & Carlos C. Crestani

  2. Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil

    Carlos E. Santos, Ricardo Benini & Carlos C. Crestani

Authors
  1. Carlos E. Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ricardo Benini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos C. Crestani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CES, RB, and CCC contributed to the conception and design of the work. CES and RB contributed to the acquisition and analysis, whereas all authors contributed to data interpretation. CES and CCC drafted the manuscript. RB critically revised the manuscript and CCC approved the final version to be published.

Corresponding author

Correspondence to Carlos C. Crestani.

Ethics declarations

Experimental procedures were carried out following the protocols approved by the Ethical Committee for the Use of Animals of the School of Pharmaceutical Science-UNESP, which comply with Brazilian and international guidelines for animal use and welfare.

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Santos, C.E., Benini, R. & Crestani, C.C. Spontaneous recovery, time course, and circadian influence on habituation of the cardiovascular responses to repeated restraint stress in rats. Pflugers Arch - Eur J Physiol 472, 1495–1506 (2020). https://doi.org/10.1007/s00424-020-02451-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-020-02451-9

Keywords

Search

Navigation