Research Article | Open Access
Stress before Puberty Exerts a Sex- and Age-Related Impact on Auditory and Contextual Fear Conditioning in the Rat
Adolescence is a period of major physical, hormonal, and psychological changes. It is also characterized by a significant increase in the incidence of psychopathologies and this increase is gender-specific. Stress during adolescence is associated with the development of psychiatric disorders later in life. In this study, we evaluated the impact of psychogenic stress (exposure to predator odor followed by placement on an elevated platform) experienced before puberty (days 28–30) on fear memories and hormonal response of male and female rats during adolescence and early adulthood. Stress before puberty impacted in a sex- and age-specific way on the responses to auditory and contextual fear conditioning in adolescence and adulthood: (a) increased conditioned fear to the tone in males during adolescence but not during adulthood; (b) impaired extinction to the tone in adult males; and (c) reduced freezing responses to the context in adolescent females. Stress before puberty did not influence the corticosterone levels 30 minutes after an additional stressor given in adulthood. These results indicate that stress experienced prior to puberty can exert a sex-related differential impact on fear-related behaviors displayed by individuals during late adolescence and early adulthood.
- L. Steinberg, R. Dahl, D. Keating, D. Kupfer, A. Masten, and D. Pine, “The study of developmental psychopathology in adolescence: integrating affective neuroscience with the study of context,” in Handbook of Developmental Psychopathology, D. Cicchetti, Ed., John Wiley & Sons, New York, NY, USA, 2005.
- K. M. Penza, C. Heim, and C. B. Nemeroff, “Neurobiological effects of childhood abuse: implications for the pathophysiology of depression and anxiety,” Archives of Women's Mental Health, vol. 6, no. 1, pp. 15–22, 2003.
- R. C. Kessler, “Epidemiology of women and depression,” Journal of Affective Disorders, vol. 74, no. 1, pp. 5–13, 2003.
- D. P. Farrington and R. Loeber, “Epidemiology of juvenile violence,” Child and Adolescent Psychiatric Clinics of North America, vol. 9, no. 4, pp. 733–748, 2000.
- J. N. Giedd, J. Blumenthal, N. O. Jeffries et al., “Brain development during childhood and adolescence: a longitudinal MRI study,” Nature Neuroscience, vol. 2, no. 10, pp. 861–863, 1999.
- E. R. Sowell, P. M. Thompson, C. J. Holmes, T. L. Jernigan, and A. W. Toga, “In vivo evidence for post-adolescent brain maturation in frontal and striatal regions,” Nature Neuroscience, vol. 2, no. 10, pp. 859–861, 1999.
- C. Hayward and K. Sanborn, “Puberty and the emergence of gender differences in psychopathology,” Journal of Adolescent Health, vol. 30, no. 4, supplement 1, pp. 49–58, 2002.
- R. E. Dahl, “Adolescent brain development: a period of vulnerabilities and opportunities. Keynote address,” Annals of the New York Academy of Sciences, vol. 1021, pp. 1–22, 2004.
- O. Agid, Y. Kohn, and B. Lerer, “Environmental stress and psychiatric illness,” Biomedicine and Pharmacotherapy, vol. 54, no. 3, pp. 135–141, 2000.
- R. C. Kessler and W. J. Magee, “Childhood adversities and adult depression: basic patterns of association in a US national survey,” Psychological Medicine, vol. 23, no. 3, pp. 679–690, 1993.
- C. Heim, P. M. Plotsky, and C. B. Nemeroff, “Importance of studying the contributions of early adverse experience to neurobiological findings in depression,” Neuropsychopharmacology, vol. 29, no. 4, pp. 641–648, 2004.
- C. M. McCormick and I. Z. Mathews, “HPA function in adolescence: role of sex hormones in its regulation and the enduring consequences of exposure to stressors,” Pharmacology Biochemistry and Behavior, vol. 86, no. 2, pp. 220–233, 2007.
- R. Fernández-Fernández, V. M. Navarro, M. L. Barreiro et al., “Effects of chronic hyperghrelinemia on puberty onset and pregnancy outcome in the rat,” Endocrinology, vol. 146, no. 7, pp. 3018–3025, 2005.
- M. G. Cunningham, S. Bhattacharyya, and F. M. Benes, “Amygdalo-cortical sprouting continues into early adulthood: implications for the development of normal and abnormal function during adolescence,” Journal of Comparative Neurology, vol. 453, no. 2, pp. 116–130, 2002.
- L. P. Spear, “The adolescent brain and age-related behavioral manifestations,” Neuroscience and Biobehavioral Reviews, vol. 24, no. 4, pp. 417–463, 2000.
- A. Avital, E. Ram, R. Maayan, A. Weizman, and G. Richter-Levin, “Effects of early-life stress on behavior and neurosteroid levels in the rat hypothalamus and entorhinal cortex,” Brain Research Bulletin, vol. 68, no. 6, pp. 419–424, 2006.
- A. Avital and G. Richter-Levin, “Exposure to juvenile stress exacerbates the behavioural consequences of exposure to stress in the adult rat,” The International Journal of Neuropsychopharmacology, vol. 8, no. 2, pp. 163–173, 2005.
- M. Tsoory, H. Cohen, and G. Richter-Levin, “Juvenile stress induces a predisposition to either anxiety or depressive-like symptoms following stress in adulthood,” European Neuropsychopharmacology, vol. 17, no. 4, pp. 245–256, 2007.
- M. Tsoory and G. Richter-Levin, “Learning under stress in the adult rat is differentially affected by ‘juvenile’ or ‘adolescent’ stress,” The International Journal of Neuropsychopharmacology, vol. 9, no. 6, pp. 713–728, 2006.
- L. N. Maslova, V. V. Bulygina, and N. K. Popova, “Immediate and long-lasting effects of chronic stress in the prepubertal age on the startle reflex,” Physiology and Behavior, vol. 75, no. 1-2, pp. 217–225, 2002.
- C. M. McCormick, D. Robarts, E. Gleason, and J. E. Kelsey, “Stress during adolescence enhances locomotor sensitization to nicotine in adulthood in female, but not male, rats,” Hormones and Behavior, vol. 46, no. 4, pp. 458–466, 2004.
- C. M. McCormick, D. Robarts, K. Kopeikina, and J. E. Kelsey, “Long-lasting, sex- and age-specific effects of social stressors on corticosterone responses to restraint and on locomotor responses to psychostimulants in rats,” Hormones and Behavior, vol. 48, no. 1, pp. 64–74, 2005.
- C. Isgor, M. Kabbaj, H. Akil, and S. J. Watson, “Delayed effects of chronic variable stress during peripubertal-juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats,” Hippocampus, vol. 14, no. 5, pp. 636–648, 2004.
- J. Sala-Catala, C. Torrero, M. Regalado, M. Salas, and A. Ruiz-Marcos, “Movements restriction and alterations of the number of spines distributed along the apical shafts of layer V pyramids in motor and primary sensory cortices of the peripubertal and adult rat,” Neuroscience, vol. 133, no. 1, pp. 137–145, 2005.
- M. Kabbaj, C. Isgor, S. J. Watson, and H. Akil, “Stress during adolescence alters behavioral sensitization to amphetamine,” Neuroscience, vol. 113, no. 2, pp. 395–400, 2002.
- G. E. Hodes and T. J. Shors, “Distinctive stress effects on learning during puberty,” Hormones and Behavior, vol. 48, no. 2, pp. 163–171, 2005.
- R. E. Bowman, K. D. Beck, and V. N. Luine, “Chronic stress effects on memory: sex differences in performance and monoaminergic activity,” Hormones and Behavior, vol. 43, no. 1, pp. 48–59, 2003.
- R. E. Bowman, “Stress-induced changes in spatial memory are sexually differentiated and vary across the lifespan,” Journal of Neuroendocrinology, vol. 17, no. 8, pp. 526–535, 2005.
- R. E. Bowman, N. J. Maclusky, S. E. Diaz, M. C. Zrull, and V. N. Luine, “Aged rats: sex differences and responses to chronic stress,” Brain Research, vol. 1126, no. 1, pp. 156–166, 2006.
- T. J. Shors, “Stressful experience and learning across the lifespan,” Annual Review of Psychology, vol. 57, pp. 55–85, 2006.
- R. L. Roof, “Neonatal exogenous testosterone modifies sex difference in radial arm and Morris water maze performance in prepubescent and adult rats,” Behavioural Brain Research, vol. 53, no. 1-2, pp. 1–10, 1993.
- K. D. Beck and V. N. Luine, “Sex differences in behavioral and neurochemical profiles after chronic stress: role of housing conditions,” Physiology and Behavior, vol. 75, no. 5, pp. 661–673, 2002.
- C. D. Conrad, K. A. Grote, R. J. Hobbs, and A. Ferayorni, “Sex differences in spatial and non-spatial Y-maze performance after chronic stress,” Neurobiology of Learning and Memory, vol. 79, no. 1, pp. 32–40, 2003.
- E. Kitraki, O. Kremmyda, D. Youlatos, M. N. Alexis, and C. Kittas, “Gender-dependent alterations in corticosteroid receptor status and spatial performance following 21 days of restraint stress,” Neuroscience, vol. 125, no. 1, pp. 47–55, 2004.
- R. E. Bowman, M. C. Zrull, and V. N. Luine, “Chronic restraint stress enhances radial arm maze performance in female rats,” Brain Research, vol. 904, no. 2, pp. 279–289, 2001.
- E. L. Weiss, J. G. Longhurst, and C. M. Mazure, “Childhood sexual abuse as a risk factor for depression in women: psychosocial and neurobiological correlates,” American Journal of Psychiatry, vol. 156, no. 6, pp. 816–828, 1999.
- S. Maren, “Nuerobiology of Pavlovian fear conditioning,” Annual Review of Neuroscience, vol. 24, pp. 897–931, 2001.
- I. C. Weiss, C. R. Pryce, A. L. Jongen-Rêlo, N. I. Nanz-Bahr, and J. Feldon, “Effect of social isolation on stress-related behavioural and neuroendocrine state in the rat,” Behavioural Brain Research, vol. 152, no. 2, pp. 279–295, 2004.
- T. A. Kosten, M. J. D. Miserendino, J. C. Bombace, H. J. Lee, and J. J. Kim, “Sex-selective effects of neonatal isolation on fear conditioning and foot shock sensitivity,” Behavioural Brain Research, vol. 157, no. 2, pp. 235–244, 2005.
- T. A. Kosten, H. J. Lee, and J. J. Kim, “Early life stress impairs fear conditioning in adult male and female rats,” Brain Research, vol. 1087, no. 1, pp. 142–150, 2006.
- J. Lehmann, C. R. Pryce, D. Bettschen, and J. Feldon, “The maternal separation paradigm and adult emotionality and cognition in male and female Wistar rats,” Pharmacology Biochemistry and Behavior, vol. 64, no. 4, pp. 705–715, 1999.
- V. Luine, C. Martinez, M. Villegas, A. M. Magariños, and B. S. McEwen, “Restraint stress reversibly enhances spatial memory performance,” Physiology and Behavior, vol. 59, no. 1, pp. 27–32, 1996.
- V. Luine, M. Villegas, C. Martinez, and B. S. McEwen, “Repeated stress causes reversible impairments of spatial memory performance,” Brain Research, vol. 639, no. 1, pp. 167–170, 1994.
- M. I. Cordero, C. Venero, N. D. Kruyt, and C. Sandi, “Prior exposure to a single stress session facilitates subsequent contextual fear conditioning in rats: evidence for a role of corticosterone,” Hormones and Behavior, vol. 44, no. 4, pp. 338–345, 2003.
- J. W. Rudy, K. Kuwagama, and C. R. Pugh, “Isolation reduces contextual but not auditory-cue fear conditioning: a role for endogenous opioids,” Behavioral Neuroscience, vol. 113, no. 2, pp. 316–323, 1999.
- C. R. Pugh, D. Tremblay, M. Fleshner, and J. W. Rudy, “A selective role for corticosterone in contextual-fear conditioning,” Behavioral Neuroscience, vol. 111, no. 3, pp. 503–511, 1997.
- M. Fleshner, C. R. Pugh, D. Tremblay, and J. W. Rudy, “DHEA-S selectively impairs contextual-fear conditioning: support for the antiglucocorticoid hypothesis,” Behavioral Neuroscience, vol. 111, no. 3, pp. 512–517, 1997.
- C. R. Pugh, M. Fleshner, and J. W. Rudy, “Type II glucocorticoid receptor antagonists impair contextual but not auditory-cue fear conditioning in juvenile rats,” Neurobiology of Learning and Memory, vol. 67, no. 1, pp. 75–79, 1997.
- J. J. Kim and M. S. Fanselow, “Modality-specific retrograde amnesia of fear,” Science, vol. 256, no. 5057, pp. 675–677, 1992.
- J. E. LeDoux, “Brain mechanisms of emotion and emotional learning,” Current Opinion in Neurobiology, vol. 2, no. 2, pp. 191–197, 1992.
- L. Calandreau, A. Desmedt, L. Decorte, and R. Jaffard, “A different recruitment of the lateral and basolateral amygdala promotes contextual or elemental conditioned association in Pavlovian fear conditioning,” Learning and Memory, vol. 12, no. 4, pp. 383–388, 2005.
- S. L. Andersen and M. H. Teicher, “Delayed effects of early stress on hippocampal development,” Neuropsychopharmacology, vol. 29, no. 11, pp. 1988–1993, 2004.
- T. R. Insel, L. P. Miller, and R. E. Gelhard, “The ontogeny of excitatory amino acid receptors in rat forebrain—I. -methyl--aspartate and quisqualate receptors,” Neuroscience, vol. 35, no. 1, pp. 31–43, 1990.
- J. Shumake, D. Barrett, and F. Gonzalez-Lima, “Behavioral characteristics of rats predisposed to learned helplessness: reduced reward sensitivity, increased novelty seeking, and persistent fear memories,” Behavioural Brain Research, vol. 164, no. 2, pp. 222–230, 2005.
- F. A. Henn and E. Edwards, “Animal models in the sutdy of genetic factors in human psychopathology,” in Genetic Studies in Affective Disorders: Overview of Basic Methods, Current Directions and Critical Research Issues, D. F. Papolos and H. M. Lachman, Eds., pp. 177–192, John Wiley & Sons, New York, NY, USA, 1994.
- J. Shumake, A. Poremba, E. Edwards, and F. Gonzalez-Lima, “Congenital helpless rats as a genetic model for cortex metabolism in depression,” NeuroReport, vol. 11, no. 17, pp. 3793–3798, 2000.
- J. Shumake, N. Conejo-Jimenez, H. Gonzalez-Pardo, and F. Gonzalez-Lima, “Brain differences in newborn rats predisposed to helpless and depressive behavior,” Brain Research, vol. 1030, no. 2, pp. 267–276, 2004.
- C. G. van Eden, J. M. Kros, and H. B. M. Uylings, “The development of the rat prefrontal cortex: its size and development of connections with thalamus, spinal cord and other cortical areas,” in Progress in Brain Research, the Prefrontal Cortex: Its Structure, Function and Pathology, H. B. M. Uylings, C. G. van Eden, J. P. C. de Bruin, M. A. Corner, and M. G. P. Feenstra, Eds., pp. 169–183, Elsevier, Amsterdam, The Netherlands, 1990.
- N. B. Farber, D. F. Wozniak, M. T. Price et al., “Age-specific neurotoxicity in the rat associated with NMDA receptor blockade: potential relevance to schizophrenia?” Biological Psychiatry, vol. 38, no. 12, pp. 788–796, 1995.
- A. Kalsbeek, P. Voorn, R. M. Buijs, C. W. Pool, and H. B. M. Uylings, “Development of the dopaminergic innervation in the prefrontal cortex of the rat,” Journal of Comparative Neurology, vol. 269, no. 1, pp. 58–72, 1988.
- C. A. Leslie, M. W. Robertson, A. J. Cutler, and J. P. Bennett Jr., “Postnatal development of dopamine receptors in the medial prefrontal cortex, striatum and nucleus accumbens of normal and neonatal 6-hydroxydopamine treated rats: a quantitative autoradiographic analysis,” Developmental Brain Research, vol. 62, no. 1, pp. 109–114, 1991.
- C. L. Coulter, H. K. Happe, and L. C. Murrin, “Postnatal development of the dopamine transporter: a quantitative autoradiographic study,” Developmental Brain Research, vol. 92, no. 2, pp. 172–181, 1996.
- E. Gould, N. J. Woolf, and L. L. Butcher, “Postnatal development of cholinergic neurons in the rat: I. Forebrain,” Brain Research Bulletin, vol. 27, no. 6, pp. 767–789, 1991.
Copyright © 2007 Maria Toledo-Rodriguez and Carmen Sandi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.