Hostname: page-component-788cddb947-tr9hg Total loading time: 0 Render date: 2024-10-15T01:47:24.709Z Has data issue: false hasContentIssue false

Prenatal stress produces sex-specific changes in depression-like behavior in rats: implications for increased vulnerability in females

Published online by Cambridge University Press:  08 July 2015

H. M. Sickmann*
Affiliation:
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark H. Lundbeck, Synaptic Transmission, Valby, Denmark Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
T. S. Arentzen
Affiliation:
H. Lundbeck, Synaptic Transmission, Valby, Denmark
T. B. Dyrby
Affiliation:
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
N. Plath
Affiliation:
H. Lundbeck, Synaptic Transmission, Valby, Denmark
M. P. Kristensen
Affiliation:
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
*
*Address for correspondence: H. M. Sickmann, Department of Drug Design and Pharmacology, Jagtvej 160, DK-2100 Copenhagen Ø, Denmark. (Email hellesickmann@hotmail.com)

Abstract

Stress during rat gestation can elicit depression-like physiological and behavioral responses in the offspring. However, human clinical depression is more prevalent among females than males. Accordingly, we examined how repeated variable prenatal stress (PS) alters rat anxiety- and depression-like behavior as well as circadian patterning of motor activity in both male and female offspring. For this purpose, we exposed pregnant Sprague–Dawley rats to multiple stressors during gestational days 13–21. Subsequently, we monitored locomotor and rearing/climbing activities in home-like cages for 24 h and measured anxiety- (elevated plus maze, EPM) and depression-like (forced swim test, FST) behaviors in the offspring at a young adult age. As a stressful event later in life (in addition to PS) may be needed to actually trigger an episode of clinical depression, half of the animals were exposed to an acute stressor (elevated platform) before EPM testing. Dams exposed to the stressor battery had increased plasma corticosterone levels compared with controls. Male PS offspring displayed changes in locomotor and rearing/climbing activity relative to controls. Additionally, anxiety measures in the EPM were affected in control animals after acute stressor exposure, however, this response was blunted in PS offspring. Moreover, FST immobility, as an indicator of depressive-like behavior, was increased in female but not male PS rats. Altogether, our results identify both sex- and circadian phase-specific effects of PS. These findings indicate that the PS rat model reflects multiple clinical depression characteristics, including elevated female vulnerability.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Kleinhaus, K, Harlap, S, Perrin, M, et al. Prenatal stress and affective disorders in a population birth cohort. Bipolar Disord. 2013; 15, 9299.Google Scholar
2. Huizink, AC, Robles de Medina, PG, Mulder, EJ, Visser, GH, Buitelaar, JK. Stress during pregnancy is associated with developmental outcome in infancy. J Child Psychol Psychiatry. 2003; 44, 810818.Google Scholar
3. Secoli, SR, Teixeira, NA. Chronic prenatal stress affects development and behavioral depression in rats. Stress. 1998; 2, 273280.Google Scholar
4. Morley-Fletcher, S, Darnaudery, M, Koehl, M, et al. Prenatal stress in rats predicts immobility behavior in the forced swim test. Effects of a chronic treatment with tianeptine. Brain Res. 2003; 989, 246251.CrossRefGoogle ScholarPubMed
5. Zuena, AR, Mairesse, J, Casolini, P, et al. Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats. PLoS One. 2008; 3, e2170.Google Scholar
6. Brunton, PJ, Russell, JA. Prenatal social stress in the rat programmes neuroendocrine and behavioural responses to stress in the adult offspring: sex-specific effects. J Neuroendocrinol. 2010; 22, 258271.Google Scholar
7. Morley-Fletcher, S, Mairesse, J, Soumier, A, et al. Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats. Psychopharmacology (Berl). 2011; 217, 301313.Google Scholar
8. Duncan, WC, Pettigrew, KD, Gillin, JC. REM architecture changes in bipolar and unipolar depression. Am J Psychiatry. 1979; 136, 14241427.Google ScholarPubMed
9. Emens, J, Lewy, A, Kinzie, JM, Arntz, D, Rough, J. Circadian misalignment in major depressive disorder. Psychiatry Res. 2009; 168, 259261.CrossRefGoogle ScholarPubMed
10. Dugovic, C, Maccari, S, Weibel, L, Turek, FW, van Reeth, O. High corticosterone levels in prenatally stressed rats predict persistent paradoxical sleep alterations. J Neurosci. 1999; 19, 86568664.CrossRefGoogle ScholarPubMed
11. Markham, JA, Taylor, AR, Taylor, SB, Bell, DB, Koenig, JI. Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat. Front Behav Neurosci. 2010; 4, 173.Google Scholar
12. Abdul Aziz, NH, Kendall, DA, Pardon, MC. Prenatal exposure to chronic mild stress increases corticosterone levels in the amniotic fluid and induces cognitive deficits in female offspring, improved by treatment with the antidepressant drug amitriptyline. Behav Brain Res. 2012; 231, 2939.Google Scholar
13. Mairesse, J, Silletti, V, Laloux, C, et al. Chronic agomelatine treatment corrects the abnormalities in the circadian rhythm of motor activity and sleep/wake cycle induced by prenatal restraint stress in adult rats. Int J Neuropshychopharmacol. 2013; 16, 323338.Google Scholar
14. Armario, A. The hypothalamic-pituitary-adrenal axis: what can it tell us about stressors? CNS Neurol Disord Drug Targets. 2006; 5, 485501.Google Scholar
15. Daviu, N, Rabasa, C, Nadal, R, Armario, A. Comparison of the effects of single and daily repeated immobilization stress on resting activity and heterotypic sensitization of the hypothalamic-pituitary-adrenal axis. Stress. 2014; 17, 176185.Google Scholar
16. Koenig, JI, Elmer, GI, Shepard, PD, et al. Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia. Behav Brain Res. 2005; 156, 251261.CrossRefGoogle ScholarPubMed
17. Emack, J, Kostaki, A, Walker, CD, Matthews, SG. Chronic maternal stress affects growth, behaviour and hypothalamo-pituitary-adrenal function in juvenile offspring. Horm Behav. 2008; 54, 514520.CrossRefGoogle ScholarPubMed
18. Weinstock, M. Gender differences in the effects of prenatal stress on brain development and behaviour. Neurochem Res. 2007; 32, 17301740.Google Scholar
19. Darnaudery, M, Maccari, S. Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev. 2008; 57, 571585.Google Scholar
20. Baker, S, Bielajew, C. Influence of housing on the consequences of chronic mild stress in female rats. Stress. 2007; 10, 283293.CrossRefGoogle ScholarPubMed
21. Brocardo, PS, Boehme, F, Patten, AR, et al. Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: protective effects of voluntary physical exercise. Neuropharmacology. 2012; 62, 16071608.CrossRefGoogle Scholar
22. Suo, L, Zhao, L, Si, J, et al. Predictable chronic mild stress in adolescence increases resilience in adulthood. Neuropsychopharmacology. 2013; 38, 13871400.CrossRefGoogle ScholarPubMed
23. Walf, AA, Frye, CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007; 2, 322328.Google Scholar
24. Detke, MJ, Rickels, M, Lucki, I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology (Berl). 1995; 121, 6672.CrossRefGoogle ScholarPubMed
25. Borsini, F, Meli, A. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology (Berl). 1988; 94, 147160.Google Scholar
26. Bielajew, C, Konkle, ATM, Kentner, AC, et al. Strain and gender specific effects in the forced swim test: effects of previous stress exposure. Stress. 2003; 6, 269280.Google Scholar
27. Szuran, T, Zimmerman, E, Pliska, V, Pfister, HP, Welzl, H. Prenatal stress effects on exploratory activity and stress-induced analgesia in rats. Dev Psychobiol. 1991; 24, 361372.Google Scholar
28. Bourke, CH, Capello, CF, Rogers, SM, et al. Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment. Psychopharmacology (Berl). 2013; 228, 231241.CrossRefGoogle ScholarPubMed
29. Weller, A, Glaubman, H, Yehuda, S, Caspy, T, Ben-Uria, Y. Acute and repeated gestational stress affect offspring learning and activity in rats. Physiol Behav. 1988; 43, 139143.Google Scholar
30. Guo, A, Nappi, RE, Criscuolo, M, et al. Effect of chronic intermittent stress on rat pregnancy and postnatal development. Eur J Obstet Gynecol Reprod Biol. 1993; 51, 4145.Google Scholar
31. Berger, MA, Barros, VG, Sarchi, MI, Tarazi, FI, Antonelli, MC. Long-term effects of prenatal stress on dopamine and glutamate recptors in the adult rat brain. Neurochem Res. 2002; 27, 15251533.Google Scholar
32. Pereira-Figueiredo, I, Sancho, C, Carro, J, Castellano, O, López, DE. The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatlly stressed rats of both sexes. Front Behav Neurosci. 2014; article number 260. doi: 10.3389/fnbeh.2014.00260.Google Scholar
33. Li, SX, Liu, LJ, Xu, LZ, et al. Diurnal alterations in circadian genes and peptides in major depressive disorder before and after escitalopram treatment. Psychoneuroendocrinology. 2013; 38, 27892799.Google Scholar
34. Volker, AC, Tulen, JHM, Van den Broek, WW, et al. Motor activity and autonomic cardiac functioning in major depressive disorder. J Affective Dis. 2003; 76, 2330.CrossRefGoogle Scholar
35. Fullerton, DT, Wenzel, FJ, Lohrenz, FN, Fahs, H. Circadian rhythm of adrenal cortical activity in depression. I. A comparison of depressed patients with normal subjects. Arch Gen Psychiatry. 1968; 19, 674681.Google Scholar
36. Tsuno, N, Besset, A, Ritchie, K. Sleep and depression. J Clin Psychiatry. 2005; 66, 12541269.Google Scholar
37. Urrila, AS, Karlsson, L, Kiviruusu, O, et al. Sleep complaints among adolescent outpatients with major depressive disorder. Sleep Med. 2012; 13, 816823.Google Scholar
38. Aulich, D. Escape versus exploratory activity: an interpretation of rats’ behaviour in the open field and a light-dark preference test. Behav Processes. 1976; 1, 153164.Google Scholar
39. Sun, H, Jia, N, Guan, L, et al. Involvement of NR1, NR2A different expression in brain regions in anxiety-like behavior of prenatally stressed offspring. Behav Brain Res. 2013; 257, 17.Google Scholar
40. Abe, H, Hidaka, N, Kawagoe, C, et al. Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis. Neurosci Res. 2007; 59, 145151.CrossRefGoogle ScholarPubMed
41. Fride, E, Dan, Y, Feldon, J, Halevy, G, Weinstock, M. Effects of prenatal stress on vulnerability to stress in prepubertal and adult rats. Physiol Behav. 1986; 37, 681687.Google Scholar
42. Vallee, M, Mayo, W, Dellu, F, et al. Prenatal stress induces high anxiety and postnatal handling induces low anxiety in adult offspring: correlation with stress-induced corticosterone secretion. J Neurosci. 1997; 17, 26262636.Google Scholar
43. Huang, Y, Chen, S, Xu, H, et al. Pre-gestational stress alters stress-response of pubertal offspring rat in sexually dimorphic and hemispherically asymmetric manner. BMC Neurosci. 2013; 14, 67.CrossRefGoogle ScholarPubMed
44. Mendez, N, Abarzua-Catalan, L, Vilches, N, et al. Timed maternal melatonin treatment reverses circadian disruption of the fetal adrenal clock imposed by exposure to constant light. PLoS One. 2012; 7, e42713.Google Scholar
45. Pollack, MH. Comorbid anxiety and depression. J Clin Psychiatry. 2005; 66, 2229.Google ScholarPubMed
46. Moffitt, TE, Harrington, H, Caspi, A, et al. Depression and generalized anxiety disorder: cumulative and sequential comorbidity in a birth cohort followed prospectively to age 32 years. Arch Gen Psychiatry. 2007; 64, 651660.CrossRefGoogle Scholar
47. Wakshlak, A, Weinstock, M. Neonatal handling reverses behavioral abnormalities induced in rats by prenatal stress. Physiol Behav. 1990; 48, 289292.Google Scholar
48. Guan, L, Jia, N, Zhao, X, et al. The involvement of ERK/CREB/Bcl-2 in depression-like behavior in prenatally stressed offspring rats. Brain Res Bull. 2013; 99, 18.Google Scholar
49. Whishaw, IQ, Gharbawie, OA, Clark, BJ, Lehmann, H. The exploratory behavior of rats in an open environment optimizes security. Behav Brain Res. 2006; 171, 230239.CrossRefGoogle Scholar
50. Barros, VG, Rodriguez, P, Martijena, ID, et al. Prenatal stress and early adoption effects on benzodiazepine receptors and anxiogenic behavior in the adult rat brain. Synapse. 2006; 60, 609618.CrossRefGoogle ScholarPubMed
51. Frye, CA, Petralia, SM, Rhodes, ME. Estrous cycle and sex differences in performance on anxiety tasks coincide with increases in hippocampal progesterone and 3alpha,5alpha-THP. Pharmacol Biochem Behav. 2000; 67, 587596.Google Scholar
52. Ravenelle, R, Neugebauer, NM, Niedzielak, T, Donaldson, ST. Sex differences in diazepam effects and parvalbumin-positive GABA neurons in trait anxiety Long Evans rats. Behav Brain Res. 2014; 270C, 6874.CrossRefGoogle Scholar
53. Katz, RJ, Roth, KA, Carrol, BJ. Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev. 1981; 5, 247251.Google Scholar
54. Russel, A. Relationships between exploratory behavior and fear: a review. Br J Psychol. 1973; 64, 417433.Google Scholar
55. Joshi, JC, Ray, A, Gulati, K. Differential modulatory effects of morphine on acute and chronic stress induced neurobehavioral and cellular markers in rats. Eur J Pharmacol. 2014; 729, 1721.Google Scholar
56. Padovan, CM, Guimaraes, FS. Restraint-induced hypoactivity in an elevated plus-maze. Braz J Med Biol Res. 2000; 33, 7983.Google Scholar
57. Porsolt, RD, Le, PM, Jalfre, M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977; 266, 730732.Google Scholar
58. Kitada, Y, Miyauchi, T, Satoh, A, Satoh, S. Effects of antidepressants in the rats forced swimming test. Eur J Pharmacol. 1981; 72, 145152.Google Scholar
59. Castagne, V, Moser, P, Roux, S, Porsolt, RD. Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Curr Protoc Neurosci. 2011; 8.10A (suppl. 55), 114.Google Scholar
60. Alonso, SJ, Arevalo, R, Afonso, D, Rodriguez, M. Effects of maternal stress during pregnancy on forced swimming behavior of the offspring. Physiol Behav. 1991; 50, 511517.Google Scholar
61. Van den Hove, DL, Kenis, G, Brass, A, et al. Vulnerability versus resilience to prenatal stress in male and female rats; implications from gene expression profiles in the hippocampus and frontal cortex. Eur Neuropsychopharmacol. 2013; 23, 12261246.Google Scholar