We report here our studies of the neuroendocrine mechanisms underlying the development of an anxiety-like state in female rats at different phases of the estrous cycle (blood estradiol level) in a stress–restress post-traumatic stress disorder (PTSD) model. Quantitative immunocytochemical methods were used to demonstrate an increase in corticoliberin expression in the paraventricular nucleus (PVN) of the hypothalamus in female rats 10 days after restress in all experimental groups. On post-restress day 30, the level of corticoliberin expression in the PVN of the hypothalamus decreased to the level seen in the control group. A significant increase in vasopressin immunoreactivity during development of the anxiety-like state was seen only in the PVN of the hypothalamus in female rats in the estrus phase (low estradiol level) at the moment of severe combined stress in the stress–restress model. Thus, the most significant changes in the neuroendocrine system of the hypothalamus was seen in female rats subjected to stress in the estrus phase, this consisting of a sharp decrease in the endogenous plasma estradiol level. Hyperactivity of the hypothalamic component of the vasopressinergic system can evidently be regarded as one of the mechanisms forming the experimental anxious PTSD-like state in female rats in the stress–restress model.
Similar content being viewed by others
References
V. M. Voloshin, Post-Traumatic Stress Disorder. Phenomenology, Clinical Aspects, Classification, Dynamics, and Contemporary Approaches to Psychopharmacotherapy, Anakharsis, Moscow (2005).
S. B. Kazakova and N. S. Sapronov, “The central effects of estrogens and their selective modulators,” in: Psychoneuroendocrinology, P. D. Shabanov and N. S. Sapronov (eds.), Inform-Navigator, St. Petersburg (2010), pp. 360–415.
V. I. Mironova and E. A. Rybnikova, “Stable modifications to the expression of neurohormones in the rat hypothalamus in a model of post-traumatic stress disorder,” Ros. Fiziol. Zh., 94, No. 11, 1277–1284 (2008).
N. E. Ordyan, S. G. Pivina, Yu. O. Fedotova, and V. V. Rakitskaya, “Formation of an anxious-depressive state in an experimental model of post-traumatic stress disorder in prenatally stressed female rats,” Ros. Fiziol. Zh., 97, No. 11, 1187–1195 (2011).
S. G. Pivina, V. V. Rakitskaya, I. V. Smolenskii, et al., “Modification of neurohormone expression in the hypothalamus in prenatally stressed male rats in a model of post-traumatic stress disorder,” Zh. Evolyuts. Biokhim. Fiziol., 50, No. 4, 305–311 (2014).
L. Arborelius, M. J. Owens, P. M. Plotsky, and C. B. Nemeroff, “The role of corticotropin-releasing factor in depression and anxiety disorders,” J. Endocrinol., 160, No. 1, 1–12 (1999).
C. R. Bailey, E. Cordell, S. M. Sobin, and A. Neumeister, “Recent progress in understanding the pathophysiology of post-traumatic stress disorder,” CNS Drugs, 27, No. 3, 221–232 (2013).
G. D. Bremner, I. Licono, and A. Darnell, “Elevated corticotropin-releasing factor concentration in posttraumatic stress disorders,” Am. J. Psychiatry, 154, No. 5, 624–629 (1997).
N. Breslau, “Gender differences in trauma and posttraumatic stress disorder,” J. Gend. Specif. Med., 5, No. 1, 34–40 (2002).
H. Cohen and R. Yehuda, “Gender differences in animal models of posttraumatic stress disorder,” Dis. Markers, 30, No. 2–3, 141–150 (2011).
N. P. Daskalakis, A. Lehrner, and R. Yehuda, “Endocrine aspects of post-traumatic stress disorder and implications for diagnosis and treatment,” Endocrinol. Metab. Clin. North Am., 42, No. 3, 503–513 (2013).
C. S. De Kloet, E. Vermetten, E. Geuze, et al., “Elevated plasma arginine vasopressin levels in veterans with posttraumatic stress disorder,” J. Psychiatr. Res., 42, No. 3, 192–198 (2008).
C. S. De Kloet, E. Vermetten, C. J. Heijnen, et al., “Enhanced cortisol suppression in response to dexamethasone administration in traumatized veterans with and without posttraumatic stress disorder,” Psychoneuroendocrinology, 32, No. 3, 215–226 (2007).
M. I. Furuta, T. Numakawa, S. Chiba, et al., “Estrogen, predominantly via estrogen receptor α, attenuates postpartum-induced anxietyand depression-like behaviors in female rats,” Endocrinology, 154, No. 10, 3807–3816 (2013).
G. E. Gillies, E. A. Linton, and P. J. Lowry, “Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin,” Nature, 299, No. 5881, 355–357 (1982).
G. Griebel, J. Stemmelin, C. S. Gal, and P. Soubrie, “Non-peptide vasopressin V1b antagonist as potential drugs for the treatment of stress-related disorders,” Curr. Pharm. Des., 11, No. 12, 1549–1559 (2005).
T. I. Hajszan, K. Szigeti-Buck, N. L. Sallam, et al., “Effects of estradiol on learned helplessness and associated remodeling of hippocampal spine synapses in female rats,” Biol. Psychiatry, 67, No. 2, 168–174 (2010).
F. Holsboer, “Neuroendocrinology of mood disorders,” in: Psychophar macology: the Fourth Generation of Progress, F. E. Bloom and D. Kupfer (eds.), Raven Press, New York (1995), Chapter 83, pp. 957–970.
F. Holsboer and M. Ising, “Central CRH system in depression and anxiety – evidence from clinical studies with CRH1 receptor antagonists,” Eur. J. Pharmacol., 583, No. 2–3, 350–357 (2008).
C. I. Isgor, M. Cecchi, M. Kabbaj, et al., “Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates the neuroendocrine response to stress and is regulated by corticosterone,” Neuroscience, 121, No. 4, 837–845 (2003).
J. W. Kaskow, D. Baker, and T. D. Geracioti, “Corticotropinreleasing hormone in depression and post-traumatic stress disorder,” Peptides, 22, 845–851 (2001).
R. C. Kessler, “Epidemiology of women and depression,” J. Affect. Disord., 74, No. 1, 5–13 (2003).
I. Liberzon, M. Krstov, and E. A. Young, “Stress-restress: effects on ACTH and fast feedback,” Psychoneuroendocrinology, 22, No. 6, 443–453 (1997).
X. M. Ma, A. Levy, and S. L. Lightman, “Emergence of an isolated arginine vasopressin (AVP) response to stress alter repeated restraint: a study of both AVP and corticotropin-releasing hormone messenger ribonucleic acid (RNA) and heteronuclear RNA,” Endocrinology, 138, No. 10, 4351–4357 (1997).
V. Mironova, E. Rybnikova, and S. Pivina, “Effect of inescapable stress in rodent models of depression and post-traumatic stress disorder on CRH and vasopressin immunoreactivity in the hypothalamic paraventricular nucleus,” Acta Physiol. Hung., 100, No. 4, 395–410 (2013).
R. E. Nappi, M. J. Bonneau, and S. Rivest, “Influence of the estrous cycle on c-fos and CRH gene transcription in the brain of endotoxin-challenged female rats,” Neuroendocrinology, 65, No. 1, 29–46 (1997).
C. B. Nemeroff, J. D. Bremner, E. B. Foa, et al., “Post-traumatic stress disorder: a state-of-the-science review,” J. Psychiatr. Res., 40, No. 1, 1–21 (2006).
T. R. Norman, “Prospects for the treatment of depression,” Aust. N. Z. J. Psychiatry, 40, No. 5, 394–401 (2006).
M. Olff, Y. Guzelcan, G. J. de Vries, et al., “HPA- and HPT-axis alterations in chronic post-traumatic stress disorder,” Psychoneuroendocrinology, 31, No. 10, 1220–1230 (2006).
L. Scott and T. G. Dinan, “Vasopressin as a target for antidepressant development: an assessment of available evidence,” J. Affect. Disord., 72, No. 2, 113–124 (2002).
D. Simeon, M. Knutelska, R. Yehuda, et al., “Hypothalamicpituitary-adrenal axis function in dissociative disorders, post-traumatic stress disorder, and healthy volunteers,” Biol. Psychiatry, 61, No. 8, 966–973 (2007).
C. Tsigos and G. P. Chrousos, “Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress,” J. Psychosom. Res., 53, No. 4, 865–871 (2002).
J. D. Uys, D. J. Stein, W. M. Daniels, and B. H. Harvey, “Animal models of anxiety disorders,” Curr. Psychiatry Rep., 5, No. 4, 274–281 (2003).
V. Viau and M. J. Meany, “α1 Adrenoreceptors mediate the stimulatory effects of oestrogen on stress-related hypothalamic-pituitary-adrenal activity in the female rat,” J. Neuroendocrinol., 16, No. 1, 72–78 (2004).
A. A. Walf and C. A. Frye, “Antianxiety and antidepressive behavior produced by physiological estradiol regimen may be modulated by hypothalamic-pituitary-adrenal axis activity,” Neuropsychopharmacology, 30, No. 7, 1288–1301 (2005).
M. H. Whitnall, “Distributions of pro-vasopressin expressing and pro-vasopressin deficient CRH neurons in the paraventricular hypothalamic nucleus of colchicine-treated normal and adrenalectomized rats,” J. Comp. Neurol., 275, No. 1, 13–28 (1988).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 101, No. 12, pp. 1355–1365, December, 2015.
Rights and permissions
About this article
Cite this article
Mironova, V.I., Rakitskaya, V.V., Pivina, S.G. et al. Stress-Induced Changes in Corticoliberin and Vasopressin Expression in the Hypothalamus of Female Rats in a Model of Post-Traumatic Stress Disorder. Neurosci Behav Physi 47, 449–455 (2017). https://doi.org/10.1007/s11055-017-0420-4
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-017-0420-4