Skip to main content
SpringerLink
Log in

Early maternal separation: a rodent model of depression and a prevailing human condition

  • Review
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

The early life of most mammals is spent in close contact with the mother, and for the neonate, early maternal separation is a traumatic event that, depending on various conditions, may shape its behavioral and neurochemical phenotype in adulthood. Studies on rodents demonstrated that a very brief separation followed by increased maternal care may positively affect the development of the offspring but that prolonged separation causes significant amounts of stress. The consequences of this stress (particularly the hyperreactivity of the HPA (hypothalamic–pituitary–adrenal) axis are expressed in adulthood and persist for life. Maternal separation in rodents, particularly rats, was used as a model for various psychotic conditions, especially depression. The most popular separation procedure of a 3-h daily separation from the second to the 12th postpartum day yields a depression model of high construct and predictive validity. The results of studies on maternal separation in rats and monkeys prompt a discussion of the consequences of traditional procedures in the maternity wards of developed countries where attention is focused on the hygiene of the neonates and not on their psychological needs. This alternate focus results in a drastic limitation of mother-infant contact and prolonged periods of separation. It is tempting to speculate that differences in the course and severity of various mental disorders, which are usually less prevalent in underdeveloped countries than in developed countries (as noted by Kraepelin), may be related to different modes of infant care. Only recently has so-called kangaroo mother care (establishing mother-infant skin-to-skin contact immediately after birth) become popular in developed countries. In addition to its instant benefits for the neonates, this procedure may also be beneficial for the mental health of the offspring in adulthood.

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

Similar content being viewed by others

References

  1. Alberts JR: Huddling by rat pups: ontogeny of individual and group behavior. Dev Psychobiol, 2007, 49, 22–32.

    Article  PubMed  Google Scholar 

  2. Andrews MM, Boyle JS: Transcultural concepts in nursing care, 5th edn., Kluwer/Lippincott, Williams, and Wilkins, Philadelphia, 2008, 487 pp.

    Google Scholar 

  3. Anisman H, Zaharia MD, Meaney MJ, Merali Z: Do early-life events permanently alter behavioral and hormonal responses to stressors? Int J Dev Neurosci, 1998, 16, 149–164.

    Article  CAS  PubMed  Google Scholar 

  4. Arborelius L, Eklund MB: Both long and brief maternal separation produces persistent changes in tissue levels of brain monoamines in middle-aged female rats. Neuroscience, 2007, 145, 738–750.

    Article  CAS  PubMed  Google Scholar 

  5. Arborelius L, Hawks BW, Owens MJ, Plotsky PM, Nemeroff CB: Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation. Psychopharmacology (Berl), 2004, 176, 248–255.

    Article  CAS  Google Scholar 

  6. Archer J: Rodent sex differences in emotional and related behavior. Behav Biol, 1975, 14, 451–479.

    Article  CAS  PubMed  Google Scholar 

  7. Bailoo JD, Jordan RL, Garza XJ, Tyler AN: Brief and long periods of maternal separation affect maternal behavior and offspring behavioral development in C57BL/6 mice. Dev Psychobiol, 2013 Jun 15. doi: https://doi.org/10.1002/dev.21135. [Epub ahead of print].

    Article  PubMed  Google Scholar 

  8. Barnett SA, Burn J: Early stimulation and maternal behaviour. Nature, 1967, 213, 150–152.

    Article  CAS  PubMed  Google Scholar 

  9. Bebbington PE, Bhugra D, Brugha T, Singleton N, Farrell M, Jenkins R, Lewis G, Meltzer H: Psychosis, victimisation and childhood disadvantage: evidence from the second British National Survey of Psychiatric Morbidity. Br J Psychiatry, 2004, 185, 220–226.

    Article  PubMed  Google Scholar 

  10. Belzung C, Lemoine M: Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression. Biol Mood Anxiety Disord, 2011, 1, 9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bengoetxea H, Ortuzar N, Bulnes S, Rico-Barrio I, Lafuente JV, Argandoña EG: Enriched and deprived sensory experience induces structural changes and rewires connectivity during the postnatal development of the brain. Neural Plast, 2012, 2012, 305693.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Biagini G, Pich EM, Carani C, Marrama P, Agnati LF: Postnatal maternal separation during the stress hypore-sponsive period enhances the adrenocortical response to novelty in adult rats by affecting feedback regulation in the CA1 hippocampal field. Int J Dev Neurosci, 1998, 16, 187–197.

    Article  CAS  PubMed  Google Scholar 

  13. Braun K, Lange E, Metzger M, Poeggel G: Maternal separation followed by early social deprivation affects the development of monoaminergic fiber systems in the medial prefrontal cortex of Octodon degus. Neuroscience, 2000, 95, 309–318.

    Article  CAS  PubMed  Google Scholar 

  14. Bryer JB, Nelson BA, Miller JB, Krol PA: Childhood sexual and physical abuse as factors in adult psychiatric illness. Am J Psychiatry, 1987, 144, 1426–1430.

    Article  CAS  PubMed  Google Scholar 

  15. Bystrova K, Ivanova V, Edhborg M, Matthiesen AS, Ransjö-Arvidson AB, Mukhamedrakhimov R, Kerstin Uvnäs-Moberg, Widstrm AM: Early contact versus separation: Effects on mother–infant interaction one year later. Birth, 2009, 36, 97–109.

    Article  PubMed  Google Scholar 

  16. Caldji C, Francis D, Sharma S, Plotsky PM, Meaney MJ: The effects of early rearing environment on the development of GABAA and central benzodiazepine receptor levels and novelty-induced fearfulness in the rat. Neu-ropsychopharmacology, 2000, 22, 219–229.

    Article  CAS  PubMed  Google Scholar 

  17. Calhoun JB: The ecology and sociology of the Norway rat. H.E.W. Public Health Service, Bethesda, 1962.

    Google Scholar 

  18. Charpak N, Ruiz JG, Zupan J, Cattaneo A, Figueroa Z, Tessier R, Cristo M et al.: Kangaroo Mother Care: 25 years after. Acta Paediatr, 2005, 94, 514–522.

    Article  PubMed  Google Scholar 

  19. Conde-Agudelo A, Belizán JM, Diaz-Rossello J: Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane Database Syst Rev, 2011, doi: https://doi.org/10.1002/14651858.CD002771.pub2.

  20. Cotella EM, Mestres Lascano I, Franchioni L, Levin GM, Suárez MM: Long-term effects of maternal separation on chronic stress response suppressed by amitriptyline treatment. Stress, 2013 16, 477–481.

    Article  CAS  PubMed  Google Scholar 

  21. Couto FS, Batalha VL, Valadas JS, Data-Franca J, Ribeiro JA, Lopes LV: Escitalopram improves memory deficits induced by maternal separation in the rat. Eur J Pharmacol, 2012, 15, 695, 71–75.

    Article  CAS  Google Scholar 

  22. D’Amato FR, Cabib S: Chronic exposure to a novel odor increases pups’ vocalizations, maternal care, and alters dopaminergic functioning in developing mice. Behav Neural Biol, 1987, 48, 197–205.

    Article  PubMed  Google Scholar 

  23. D’Amato FR, Cabib S, Ventura R, Orsini C: Long-term effects of postnatal manipulation on emotionality are prevented by maternal anxiolytic treatment in mice. Dev Psychobiol, 1998, 32, 225–234.

    Article  PubMed  Google Scholar 

  24. de Kloet ER, Sibug RM, Helmerhorst FM, Schmidt MV, Schmidt M: Stress, genes and the mechanism of programming the brain for later life. Neurosci Biobehav Rev, 2005, 29, 271–281.

    Article  PubMed  CAS  Google Scholar 

  25. Denenberg VH: Critical periods, stimuli input, and emotional reactivity: A theory of infantile stimulation. Psychol Rev, 1964, 71, 335–351.

    Article  CAS  PubMed  Google Scholar 

  26. Denenberg VH, Karas GG: Effects of differential infantile handling upon weight gain and mortality in the rat and mouse. Science, 1959, 130, 629–630.

    Article  CAS  PubMed  Google Scholar 

  27. Dimatelis JJ, Stein DJ, Russell VA: Behavioral changes after maternal separation are reversed by chronic constant light treatment. Brain Res, 2012, 1480, 61–71.

    Article  CAS  PubMed  Google Scholar 

  28. Durand M, Sarrieau A, Aguerre S, Mormede P, Chaouloff F: Differential effects of neonatal handling on anxiety, corticosterone response to stress, and hippocampal glucocorticoid and serotonin (5-HT)2A receptors in Lewis rats. Psychoneuroendocrinology, 1998, 23, 323–335.

    Article  CAS  PubMed  Google Scholar 

  29. Eklund MB, Arborelius L: Twice daily long maternal separations in Wistar rats decreases anxiety-like behaviour in females but does not affect males. Behav Brain Res, 2006, 172, 278–285.

    Article  PubMed  Google Scholar 

  30. Francis D, Diorio J, Liu D, Meaney MJ: Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science, 1999, 286, 1155–1158.

    Article  CAS  PubMed  Google Scholar 

  31. Francis DD, Caldji C, Champagne F, Plotsky PM, Meaney MJ: The role of corticotropin-releasing factor–norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiat, 1999, 46, 1153–1166.

    Article  CAS  PubMed  Google Scholar 

  32. Francis DD, Diorio J, Plotsky PM, Meaney MJ: Environmental enrichment reverses the effects of maternal separation on stress reactivity. J Neurosci, 2002, 22, 7840–7843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Gilbert R, Widom CS, Browne K, Fergusson D, Webb E, Janson S: Burden and consequences of child maltreatment in high-income countries. Lancet, 2009, 373, 68–81.

    Article  PubMed  Google Scholar 

  34. Greisen MH, Altar CA, Bolwig TG, Whitehead R, Wörtwein G: Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats. J Neurosci Res, 2005, 79, 772–778.

    Article  CAS  PubMed  Google Scholar 

  35. Hall FS: Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences. Crit Rev Neurobiol, 1998, 12, 129–162.

    Article  CAS  PubMed  Google Scholar 

  36. Hofer MA: Physiological responses of infant rats to separation from their mothers. Science, 1970, 168, 871–873.

    Article  CAS  PubMed  Google Scholar 

  37. Hofer MA: Studies on how early maternal separation produces behavioral change in young rats. Psychosom Med, 1975, 37, 245–264.

    Article  CAS  PubMed  Google Scholar 

  38. Hofer MA: The organization of sleep and wakefulness after maternal separation in young rats. Dev Psychobiol, 1976, 9, 189–205.

    Article  CAS  PubMed  Google Scholar 

  39. Hofer MA: The psychobiology of early attachment, Clin Neurosci Res, 2005, 15, 84–87.

    Google Scholar 

  40. Holmes A, Le Guisquet AM, Vogel E, Mollstein RA, Leman S, Belzung C: Early life genetic, epigenetic and environmental factors shaping emotionality in rodents. Neurosci Biobehav Rev, 2005, 29, 1335–1346.

    Article  PubMed  Google Scholar 

  41. Huot RL, Plotsky PM, Lenox RH, McNamara RK: Neonatal maternal separation reduces hippocampal mossy fiber density in adult Long Evans rats. Brain Res, 2002, 950, 52–63.

    Article  CAS  PubMed  Google Scholar 

  42. Huot RL, Smith MA, Plotsky PM: Alterations of maternal-infant interaction as a result of maternal separation in Long Evans rats and its behavioral and neuroendocrine consequences. Psychoneuroendocrinology, 1997, 22, Suppl 2, S173.

    Google Scholar 

  43. Huot RL, Thrivikraman KV, Meaney MJ, Plotsky PM: Development of adult ethanol preference and anxiety as a consequence of neonatal maternal separation in Long Evans rats and reversal with antidepressant treatment. Psychopharmacology (Berl), 2001, 158, 366–373.

    Article  CAS  Google Scholar 

  44. Johnston AL, File SE: Sex differences in animal tests of anxiety. Physiol Behav, 1991, 49, 245–250.

    Article  CAS  PubMed  Google Scholar 

  45. Kaffman A, Meaney M: Neurodevelopmental sequelae of postnatal maternal care in rodents: clinical and research implications of molecular insights. J Child Psychol Psychiatry, 2007, 48, 224–244.

    Article  PubMed  Google Scholar 

  46. Kalinichev M, Easterling KW, Plotsky PM, Holtzman SG: Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats. Pharmacol Biochem Behav, 2002, 73, 131–140.

    Article  CAS  PubMed  Google Scholar 

  47. Kaplow JB, Widom CS: Age of onset of child maltreatment predicts long-term mental health outcomes. J Ab-norm Psychol, 2007, 116, 176–187.

    Article  Google Scholar 

  48. Kaufman J, Charney D: Effects of early stress on brain structure and function: implications for understanding the relationship between child maltreatment and depression. Dev Psychopathol, 2001, 13, 451–471.

    Article  CAS  PubMed  Google Scholar 

  49. Khoury A, Gruber SH, Mørk A, Mathé AA: Adult life behavioral consequences of early maternal separation are alleviated by escitalopram treatment in a rat model of depression. Prog Neuropsychopharmacol Biol Psychiatry, 2006, 30, 535–540.

    Article  PubMed  CAS  Google Scholar 

  50. Kojima S, Alberts JR: Oxytocin mediates the acquisition of filial, odor-guided huddling for maternally-associated odor in preweanling rats. Horm Behav, 2011, 60, 549–558.

    Article  CAS  PubMed  Google Scholar 

  51. Kojima S, Stewart RA, Demas GE, Alberts JR: Maternal contact differentially modulates central and peripheral oxytocin in rat pups during a brief regime of mother-pup interaction that induces a filial huddling preference. J Neuroendocrinol, 2012, 24, 831–840.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kraepelin E: Comparative psychiatry (German). Zentbl Nervenheilk Psychiat, 1904, 27, 433–437.

    Google Scholar 

  53. Kuhn CM, Pauk J, Schanberg SM: Endocrine responses to mother-infant separation in developing rats. Dev Psychobiol, 1990, 23, 395–410.

    Article  CAS  PubMed  Google Scholar 

  54. Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Plotsky PM: Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor mRNA and negative feedback on the hypothalamo-pituitary-adrenal axis following neonatal maternal separation. Biol Psychiatry, 2004, 55, 367–375.

    Article  CAS  PubMed  Google Scholar 

  55. Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Meaney MJ, Plotsky PM: Long-term behavioral and neuroendocrine adaptations to adverse early experience. Progr Brain Res, 2000, 122, 81–103.

    Article  CAS  Google Scholar 

  56. Ladd CO, Owens MJ, Nemeroff CB: Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology, 1996, 137, 1212–1218.

    Article  CAS  PubMed  Google Scholar 

  57. Lajud N, Roque A, Cajero M, Gutiérrez-Ospina G, Torner L: Periodic maternal separation decreases hippo-campal neurogenesis without affecting basal corticosterone during the stress hyporesponsivriod, but alters HPA axis and coping behavior in adulthood. Psychoneuroen-docrinology, 2012, 37, 410–420.

    Article  CAS  PubMed  Google Scholar 

  58. Lehmann J, Feldon J: Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing? Rev Neurosci, 2000, 11 383–408.

    Article  CAS  PubMed  Google Scholar 

  59. Leventopoulos M, Russig H, Feldon J, Pryce CR, Opacka-Juffry J: Early deprivation leads to long-term reductions in motivation for reward and 5-HT1A binding and both effects are reversed by fluoxetine, Neurophar-macology, 2009, 56, 692–670.

    Article  CAS  Google Scholar 

  60. Levine S: Infantile experience and resistance to physiological stress. Science, 1957, 126, 405.

    Article  CAS  PubMed  Google Scholar 

  61. Levine S: Plasma-free corticosteroid response to electric shocks in rats stimulated in infancy. Science, 1962, 135, 795–796.

    Article  CAS  PubMed  Google Scholar 

  62. Lévy F, Melo AI, Galef BG Jr, Madden M, Fleming AS: Complete maternal deprivation affects social, but not spatial, learning in adult rats. Dev Psychobiol, 2003, 43, 177–191.

    Article  PubMed  Google Scholar 

  63. Lippmann M, Bress A, Nemeroff CB, Plotsky PM, Monteggia LM: Long-term behavioural and molecular alterations associated with maternal separation in rats. Eur J Neurosci, 2007, 25, 3091–3098.

    Article  PubMed  Google Scholar 

  64. Liu D, Caldji C, Sharma S, Plotsky PM, Meaney MJ: Influence of neonatal rearing conditions on stress-induced adrenocorticotropin responses and norepinep-herine release in the hypothalamic paraventricular nucleus. J Neuroendocrinol, 2000, 12, 5–12.

    Article  PubMed  Google Scholar 

  65. Liu D, Diorio J, Day JC, Francis DD, Meaney MJ: Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci, 2000, 3, 799–806.

    Article  CAS  PubMed  Google Scholar 

  66. Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S et al.: Maternal care, hippocampal glucocorticoid receptors, and hypothalamic–pituitary–adrenal responses to stress. Science, 1997, 277, 1659–1662.

    Article  CAS  PubMed  Google Scholar 

  67. Ludington-Hoe SM, Morgan K, Abouefettoh A: A clinical guideline for implementation of kangaroo care with premature infants of 30 weeks’ postmenstrual age. Adv Neonatal Care, 2008, 8, Suppl, S3–S23.

    Article  Google Scholar 

  68. MacQueen GM, Ramakrishnan K, Ratnasingan R, Chen B, Young LT: Desipramine treatment reduces the long-term behavioural and neurochemical sequelae of early-life maternal separation. Int J Neuropsychopharmacol, 2003, 6, 391–396.

    Article  CAS  PubMed  Google Scholar 

  69. Maniam J, Morris MJ: Palatable cafeteria diet ameliorates anxiety and depression-like symptoms following an adverse early environment. Psychoneuroendocrinology, 2010, 35, 717–728.

    Article  CAS  PubMed  Google Scholar 

  70. Marco EM, Adriani W, Llorente R, Laviola G, Viveros MP: Detrimental psychophysiological effects of early maternal deprivation in adolescent and adult rodents: altered responses to cannabinoid exposure. Neurosci Biobehav Rev, 2009, 33, 498–507.

    Article  CAS  PubMed  Google Scholar 

  71. Marmendal M, Roman E, Eriksson CJ, Nylander I, Fahlke C: Maternal separation alters maternal care, but has minor effects on behavior and brain opioid peptides in adult offspring. Dev Psychobiol, 2004, 45, 140–152.

    Article  CAS  PubMed  Google Scholar 

  72. Matthews K, Robbins TW: Early experience as a determinant of adult behavioural responses to reward: the effects of repeated maternal separation in the rat. Neurosci Biobehav Rev, 2003, 27, 45–55.

    Article  PubMed  Google Scholar 

  73. Matthews K, Wilkinson LS, Robbins TW: Repeated maternal separation of preweanling rats attenuates behavioral responses to primary and conditioned incentives in adulthood. Physiol Behav, 1996, 59, 99–107.

    Article  CAS  PubMed  Google Scholar 

  74. McEwen BS: Early life influences on life-long patterns of behavior and health. Ment Retard Dev Disabil Res Rev, 2003, 9, 149–154.

    Article  PubMed  Google Scholar 

  75. McIntosh J, Anisman H, Merali Z: Short- and long-periods of neonatal maternal separation differentially affect anxiety and feeding in adult rats: gender-dependent effects. Brain Res Dev Brain Res, 1999, 113, 97–106.

    Article  CAS  PubMed  Google Scholar 

  76. Meaney MJ. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci, 2001, 24, 1161–1192.

    Article  CAS  PubMed  Google Scholar 

  77. Meaney MJ, Aitken DH, Bodnoff SR, Iny LJ, Tatarewicz JE, Sapolsky RM: Early postnatal handling alters gluco-corticoid receptor concentrations in selected brain regions. Behav Neurosci, 1985, 99, 760–765.

    Article  Google Scholar 

  78. Meaney MJ, Viau V, Bhatnagar S, Betito K, Iny LJ, O’Donnell D, Mitchell JB: Cellular mechanisms underlying the development and expression of individual differences in the hypothalamic–pituitary–adrenal stress response. J Steroid Biochem Mol Biol, 1991, 39, 265–274.

    Article  CAS  PubMed  Google Scholar 

  79. Millstein RA, Holmes A: Effects of repeated maternal separation on anxiety- and depression-related phenotypes in different mouse strains. Neurosci Biobehav Rev, 2007, 31, 3–17.

    Article  PubMed  Google Scholar 

  80. Millstein RA, Ralph RJ, Yang RJ, Holmes A: Effects of repeated maternal separation on prepulse inhibition of startle across inbred mouse strains. Genes Brain Behav, 2006, 5, 346–354.

    Article  CAS  PubMed  Google Scholar 

  81. Moldavsky D: The implication of transcultural psychiatry for clinical practice. Isr J Psychiatry Relat Sci, 2003, 40, 47–56.

    PubMed  Google Scholar 

  82. Morgan BE, Horn AR, Bergman NJ: Should neonates sleep alone? Biol Psychiatry, 2011, 70, 817–825.

    Article  PubMed  Google Scholar 

  83. Mullen PE, Martin JL, Anderson JC, Romans SE, Herbison GP: The long-term impact of the physical, emotional, and sexual abuse of children: a community study. Child Abuse Negl, 1996, 20, 7–21.

    Article  CAS  PubMed  Google Scholar 

  84. Nemeroff CB, Heim CM, Thase ME, Klein DN, Rush AJ, Schatzberg AF, Ninan PT et al.: Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc Natl Acad Sci USA, 2003, 100, 14293–14296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. NICE clinical guidelines: CG37 Postnatal care: Routine postnatal care of women and their babies. Starting successful breastfeeding., July 2006.

  86. Noorikhajavi M, Afghah S, Dadkhah A, Holakoyie K, Motamedi SH: The effect of “parental loss” under 18 on developing “MDD” in adult age. Int J Psychiatry Med, 2007, 37, 347–355.

    Article  PubMed  Google Scholar 

  87. Papaioannou A, Gerozissis K, Prokopiou A, Bolaris S, Stylianopoulou F: Sex differences in the effects of neonatal handling on the animal’s response to stress and the vulnerability for depressive behaviour. Behav Brain Res, 2002, 129, 131–139.

    Article  CAS  PubMed  Google Scholar 

  88. Parfitt DB, Walton JR, Corriveau EA, Helmreich DL: Early life stress effects on adult stress-induced corticosterone secretion and anxiety-like behavior in the C57BL/6 mouse are not as robust as initially thought. Horm Behav, 2007, 52, 417–426.

    Article  CAS  PubMed  Google Scholar 

  89. Parker KJ, Maestripieri D: Identifying key features of early stressful experiences that produce stress vulnerability and resilience in primates. Neurosci Biobehav Rev, 2010, 35, 1466–1483.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Pesonen AK, Räikkönen K, Heinonen K, Kajantie E, Forsén T, Eriksson JG: Depressive symptoms in adults separated from their parents as children: a natural experiment during World War II. Am J Epidemiol, 2007, 166, 1126–1133.

    Article  PubMed  Google Scholar 

  91. Ploj K, Roman E, Bergström L, Nylander I: Effects of neonatal handling on nociceptin/orphanin FQ and opioid peptide levels in female rats. Pharmacol Biochem Behav, 2001, 69, 173–179.

    Article  CAS  PubMed  Google Scholar 

  92. Ploj K, Roman E, Nylander I: Effects of maternal separation on brain nociceptin/orphanin FQ peptide levels in male Wistar rats.Pharmacol Biochem Behav, 2002, 73, 123–129.

    Article  CAS  PubMed  Google Scholar 

  93. Ploj K, Roman E, Nylander I: Long-term effects of short and long periods of maternal separation on brain opioid peptide levels in male Wistar rats. Neuropeptides, 2003, 37, 149–156.

    Article  CAS  PubMed  Google Scholar 

  94. Plotsky PM, Bradley CC, Anand KJS: Behavioral and neuroendocrine consequences of neo-natal stress. In: Pain in Neonates, Eds. Anand KJS, McGrath PJ, Stevens BJ, Elsevier Science, Amsterdam, 2000, 77–99.

    Google Scholar 

  95. Plotsky PM, Meaney MJ: Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Brain Res Mol Brain Res, 1993, 18, 195–200.

    Article  CAS  PubMed  Google Scholar 

  96. Pryce CR, Aubert Y, Maier C, Pearce PC, Fuchs E: The developmental impact of prenatal stress, prenatal dexamethasone and postnatal social stress on physiology, behaviour and neuroanatomy of primate offspring: Studies in rhesus macaque and common marmoset. Psycho-pharmacology (Berl), 2011, 214, 33–53.

    Article  CAS  Google Scholar 

  97. Pryce CR, Dettling AC, Spengler M, Schnell CR, Feldon J: Deprivation of parenting disrupts development of homeostatic and reward systems in marmoset monkey offspring. Biol Psychiatry, 2004, 56, 72–79.

    Article  PubMed  Google Scholar 

  98. Pryce CR, Feldon J: Long-term neurobehavioural impact of the postnatal environment in rats: manipulations, effects and mediating mechanisms. Neurosci Biobehav Rev, 2003, 27, 57–71.

    Article  PubMed  Google Scholar 

  99. Renard GM, Rivarola MA, Suárez MM: Sexual dimorphism in rats: effects of early maternal separation and variable chronic stress on pituitary-adrenal axis and behavior. Int J Dev Neurosci, 2007, 25, 373–379.

    Article  CAS  PubMed  Google Scholar 

  100. Roceri M, Cirulli F, Pessina C, Peretto P, Racagni G, Riva MA: Postnatal repeated maternal deprivation produces age-dependent changes of brain-derived neurotrophic factor expression in selected rat brain regions. Biol Psychiatry, 2004, 55, 708–714.

    Article  CAS  PubMed  Google Scholar 

  101. Rodgers C: Why Kangaroo Mother Care should be standard for all newborns. J Midwifery Womens Health, 2013, 58, 249–252.

    Article  PubMed  Google Scholar 

  102. Rüedi-Bettschen D, Feldon J, Pryce CR: The impaired coping induced by early deprivation is reversed by chronic fluoxetine treatment in adult Fischer rats. Behav Pharmacol, 2004, 15, 413–421.

    Article  PubMed  Google Scholar 

  103. Rüedi-Bettschen D, Zhang W, Russig H, Ferger B, Weston A, Pedersen EM, Feldon J, Pryce CR: Early deprivation leads to altered behavioural, autonomic and endocrine responses to environmental challenge in adult Fischer rats. Eur J Neurosci, 2006, 24, 2879–2893.

    Article  PubMed  Google Scholar 

  104. Sánchez MM, Ladd CO, Plotsky PM: Early adverse experience as a developmental risk factor for later psycho-pathology: evidence from rodent and primate models. Dev Psychopathol, 2001, 13, 419–449.

    Article  PubMed  Google Scholar 

  105. Sapolsky RM, Meaney MJ: Maturation of the adrenocortical stress response: neuroendocrine control mechanisms and the stress hyporesponsive period, Brain Res, 1986, 396, 64–76.

    Article  CAS  PubMed  Google Scholar 

  106. Schmidt MV: Animal models for depression and the mismatch hypothesis of disease. Psychoneuroendocrinology, 2011, 36, 330–338.

    Article  PubMed  Google Scholar 

  107. Schmidt MV, Wang XD, Meijer OC: Early life stress paradigms in rodents: potential animal models of depression? Psychopharmacology (Berl), 2011, 214, 131–140.

    Article  CAS  Google Scholar 

  108. Schreiber HL, Bell RW, Kufner M, Villescas R: Maternal behavior: a determinant of amphetamine toxicity in rats. Psychopharmacology (Berl), 1977, 52, 173–176.

    Article  CAS  Google Scholar 

  109. Stahl CE, Redei E, Wang Y, Borlongan CV: Behavioral, hormonal and histological stress markers of anxiety-separation in postnatal rats are reduced by prepro-thyrotropin-releasing hormone. Neurosci Lett, 2002, 15, 321, 85–89.

    Article  Google Scholar 

  110. Stanton ME, Levine S: Inhibition of infant glucocorticoid stress response: specific role of maternal cues. Dev Psychobiol, 1990, 23, 411–426.

    Article  CAS  PubMed  Google Scholar 

  111. Swinny JD, O’Farrell E, Bingham BC, Piel DA, Valentino RJ, Beck SG: Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor. Int J Neuropsychopharmacol, 2010, 13, 515–225.

    Article  CAS  PubMed  Google Scholar 

  112. Thierry B, Steru L, Chermat R, Simon P: Searching-waiting strategy: a candidate for an evolutionary model of depression? Behav Neural Biol, 1984, 41, 180–189.

    Article  CAS  PubMed  Google Scholar 

  113. Trujillo V, Masseroni ML, Levin G, Suárez MM: Tianeptine influence on plasmatic catecholamine levels and anxiety index in rats under variable chronic stress after early maternal separation. Int J Neurosci, 2009, 119, 1210–1227.

    Article  CAS  PubMed  Google Scholar 

  114. Tyrka AR, Wier L, Price LH, Ross N, Anderson GM, Wilkinson CW, Carpenter LL: Childhood parental loss and adult hypothalamic-pituitary-adrenal function. Biol Psychiatry, 2008, 63, 1147–1154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Tyrka AR, Wier L, Price LH, Ross NS, Carpenter LL: Childhood parental loss and adult psychopathology: effects of loss characteristics and contextual factors. Int J Psychiatry Med, 2008, 38, 329–344.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Velandia M, Uvnäs-Moberg K, Nissen E: Sex differences in newborn interaction with mother or father during skin-to-skin contact after Caesarean section. Acta Paediatr, 2012, 101, 360–367.

    Article  PubMed  Google Scholar 

  117. Weber BC, Manfredo HN, Rinaman L: A potential gastrointestinal link between enhanced postnatal maternal care and reduced anxiety-like behavior in adolescent rats. Behav Neurosci, 2009, 123, 1178–1184.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Weininger O:Mortality of albino rats under stress as a function of early handling. Can J Psychol, 1953, 7, 111–114.

    Article  CAS  PubMed  Google Scholar 

  119. Weinshenker D, Schroeder JP: There and back again: a tale of norepinephrine and drug addiction. Neuropsy-chopharmacology, 2007, 32, 1433–1451.

    Article  CAS  PubMed  Google Scholar 

  120. Wigger A, Neumann ID: Periodic maternal deprivation induces gender-dependent alterations in behavioral and neuroendocrine responses to emotional stress in adult rats. Physiol Behav, 1999, 66, 293–302 .

    Article  CAS  PubMed  Google Scholar 

  121. Winberg J: Mother and newborn baby: mutual regulation of physiology and behavior – a selective review. Dev Psychobiol, 2005, 47, 217–229.

    Article  PubMed  Google Scholar 

  122. Zimmerberg B, Sageser KA: Comparison of two rodent models of maternal separation on juvenile social behavior. Front Psychiatry, 2011, 2, 39. doi: https://doi.org/10.3389/fpsyt.2011.00039.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Smętna 12, PL 31-343, Poland

    Jerzy Vetulani

Authors
  1. Jerzy Vetulani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jerzy Vetulani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vetulani, J. Early maternal separation: a rodent model of depression and a prevailing human condition. Pharmacol. Rep 65, 1451–1461 (2013). https://doi.org/10.1016/S1734-1140(13)71505-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/S1734-1140(13)71505-6

Key words

Search

Navigation