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Prenatal Stress Produces Social Behavior Deficits and Alters the Number of Oxytocin and Vasopressin Neurons in Adult Rats

Neurochemical Research volume 38, pages 1479–1489 (2013)Cite this article

Abstract

The present study investigated the long-lasting effects of prenatal repeated restraint stress on social behavior and anxiety, as well as its repercussions on oxytocin (OT) and vasopressin (VP)-positive neurons of the paraventricular (PVN) and supraoptic (SON) nuclei from stressed pups in adulthood. Female Wistar rats were exposed to restraint stress in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatally non-stressed offspring raised by prenatally non-stressed mothers (NS:NS), prenatally non-stressed offspring raised by prenatally stressed mothers (S:NS), prenatally stressed offspring raised by prenatally non-stressed mothers (NS:S), prenatally stressed offspring raised by prenatally stressed mothers (S:S). As adults, male prenatally stressed offspring raised both by stressed mothers (S:S group) and non-stressed ones (NS:S group) showed impaired social memory and interaction. In addition, when both adverse conditions coexisted (S:S group), increased anxiety-like behavior and aggressiveness was observed in association with a decrease in the number of OT-positive magnocellular neurons, VP-positive magnocellular and parvocellular neurons of the PVN. The NS:S group exhibited a reduction in the amount of VP-positive magnocellular neurons compared to the S:NS. Thus, the social behavior deficits observed in the S:S and NS:S groups may be only partially associated with these alterations to the peptidergic systems. No changes were shown in the OT and VP cellular composition of the SON nucleus. Nevertheless, it is clear that a special attention should be given to the gestational period, since stressful events during this time may be related to the emergence of behavioral impairments in adulthood.

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References

  1. Ferguson JN, Young LJ, Insel TR (2002) The neuroendocrine basis of social recognition. Front Neuroendocrinol 23:200–224

    Article  PubMed  CAS  Google Scholar 

  2. Bielsky IF, Young LJ (2004) Oxytocin, vasopressin, and social recognition in mammals. Peptides 25:1565–1574

    Article  PubMed  CAS  Google Scholar 

  3. Lukas M, Neumann ID (2012) Oxytocin and vasopressin in rodent behaviors related to social dysfunctions in autism spectrum disorders. Behav Brain Res. doi:10.1016/j.bbr.2012.08.011

  4. Ebstein RP, Knafo A, Mankuta D et al (2012) The contributions of oxytocin and vasopressin pathway genes to human behavior. Horm Behav 61:359–379

    Article  PubMed  CAS  Google Scholar 

  5. Young LJ, Flanagan-Cato LM (2012) Editorial comment: oxytocin, vasopressin and social behavior. Horm Behav 61:227–229

    Article  PubMed  Google Scholar 

  6. Young KA, Gobrogge KL, Liu Y et al (2011) The neurobiology of pair bonding: insights from a socially monogamous rodent. Front Neuroendocrinol 32:53–69

    Article  PubMed  Google Scholar 

  7. Bosch OJ, Meddle SL, Beiderbeck DI et al (2005) Brain oxytocin correlates with maternal aggression: link to anxiety. J Neurosci 25:6807–6815

    Article  PubMed  CAS  Google Scholar 

  8. Goodson JL, Schrock SE, Klatt JD et al (2009) Mesotocin and nonapeptide receptors promote estrildid flocking behavior. Science 325:862–866

    Article  PubMed  CAS  Google Scholar 

  9. Winslow JT, Hastings N, Carter CS et al (1993) A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365:545–548

    Article  PubMed  CAS  Google Scholar 

  10. Todeschin AS, Winkelmann-Duarte EC, Jacob MH et al (2009) Effects of neonatal handling on social memory, social interaction, and number of oxytocin and vasopressin neurons in rats. Horm Behav 56:93–100

    Article  PubMed  CAS  Google Scholar 

  11. Tobin VA, Hashimoto H, Wacker DW et al (2010) An intrinsic vasopressin system in the olfactory bulb is involved in social recognition. Nature 464:413–417

    Article  PubMed  CAS  Google Scholar 

  12. Patin V, Lordi B, Vincent A et al (2005) Effects of prenatal stress on anxiety and social interactions in adult rats. Brain Res Dev Brain Res 160:265–274

    Article  PubMed  CAS  Google Scholar 

  13. Lee PR, Brady DL, Shapiro RA et al (2007) Prenatal stress generates deficits in rat social behavior: reversal by oxytocin. Brain Res 1156:152–167

    Article  PubMed  CAS  Google Scholar 

  14. Weller A, Glaubman H, Yehuda S et al (1988) Acute and repeated gestational stress affect offspring learning and activity in rats. Physiol Behav 43:139–143

    Article  PubMed  CAS  Google Scholar 

  15. Grimm VE, Frieder B (1987) The effects of mild maternal stress during pregnancy on the behavior of rat pups. Int J Neurosci 35:65–72

    Article  PubMed  CAS  Google Scholar 

  16. Smith BL, Wills G, Naylor D (1981) The effects of prenatal stress on rat offsprings’ learning ability. J Psychol 107:45–51

    Article  PubMed  CAS  Google Scholar 

  17. Dickerson PA, Lally BE, Gunnel E et al (2005) Early emergence of increased fearful behavior in prenatally stressed rats. Physiol Behav 86:586–593

    Article  PubMed  CAS  Google Scholar 

  18. Ward HE, Johnson EA, Salm AK et al (2000) Effects of prenatal stress on defensive withdrawal behavior and corticotropin releasing factor systems in rat brain. Physiol Behav 70:359–366

    Article  PubMed  CAS  Google Scholar 

  19. Morley-Fletcher S, Darnaudery M, Koehl M et al (2003) Prenatal stress in rats predicts immobility behavior in the forced swim test. Effects of a chronic treatment with tianeptine. Brain Res 989:246–251

    Article  PubMed  CAS  Google Scholar 

  20. Poltyrev T, Gorodetsky E, Bejar C et al (2005) Effect of chronic treatment with ladostigil (TV-3326) on anxiogenic and depressive-like behaviour and on activity of the hypothalamic-pituitary-adrenal axis in male and female prenatally stressed rats. Psychopharmacology 181:118–125

    Article  PubMed  CAS  Google Scholar 

  21. de Souza MA, Szawka RE, Centenaro LA et al (2012) Prenatal stress produces sex differences in nest odor preference. Physiol Behav 105:850–855

    Article  PubMed  Google Scholar 

  22. Del Cerro MC, Perez-Laso C, Ortega E et al (2010) Maternal care counteracts behavioral effects of prenatal environmental stress in female rats. Behav Brain Res 208:593–602

    Article  PubMed  Google Scholar 

  23. Korte SM, De Boer SF (2003) A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze. Eur J Pharmacol 463:163–175

    Article  PubMed  Google Scholar 

  24. Bhattacharya SK, Satyan KS (1997) Experimental methods for evaluation of psychotropic agents in rodents: I-Anti-anxiety agents. Indian J Exp Biol 35:565–575

    PubMed  CAS  Google Scholar 

  25. Winslow JT, Camacho F (1995) Cholinergic modulation of a decrement in social investigation following repeated contacts between mice. Psychopharmacology 121:164–172

    Article  PubMed  CAS  Google Scholar 

  26. Centenaro LA, Jaeger Mda C, Ilha J et al (2011) Olfactory and respiratory lamina propria transplantation after spinal cord transection in rats: effects on functional recovery and axonal regeneration. Brain Res 1426:54–72

    Article  PubMed  CAS  Google Scholar 

  27. Winkelmann-Duarte EC, Todeschin AS, Fernandes MC et al (2007) Plastic changes induced by neonatal handling in the hypothalamus of female rats. Brain Res 1170:20–30

    Article  PubMed  CAS  Google Scholar 

  28. Mandarim-de-Lacerda CA (2003) Stereological tools in biomedical research. An Acad Bras Cienc 75:469–486

    Article  PubMed  Google Scholar 

  29. Hogg S (1996) A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav 54:21–30

    Article  PubMed  CAS  Google Scholar 

  30. Maccari S, Piazza PV, Kabbaj M et al (1995) Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress. J Neurosci 15:110–116

    PubMed  CAS  Google Scholar 

  31. Lui CC, Wang JY, Tain YL et al (2011) Prenatal stress in rat causes long-term spatial memory deficit and hippocampus MRI abnormality: differential effects of postweaning enriched environment. Neurochem Int 58:434–441

    Article  PubMed  CAS  Google Scholar 

  32. Wu J, Song TB, Li YJ et al (2007) Prenatal restraint stress impairs learning and memory and hippocampal PKCbeta1 expression and translocation in offspring rats. Brain Res 1141:205–213

    Article  PubMed  CAS  Google Scholar 

  33. Schulz KM, Pearson JN, Neeley EW et al (2011) Maternal stress during pregnancy causes sex-specific alterations in offspring memory performance, social interactions, indices of anxiety, and body mass. Physiol Behav 104:340–347

    Article  PubMed  CAS  Google Scholar 

  34. Welberg LA, Seckl JR (2001) Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 13:113–128

    Article  PubMed  CAS  Google Scholar 

  35. Kapoor A, Petropoulos S, Matthews SG (2008) Fetal programming of hypothalamic-pituitary-adrenal (HPA) axis function and behavior by synthetic glucocorticoids. Brain Res Rev 57:586–595

    Article  PubMed  CAS  Google Scholar 

  36. Weinstock M (2008) The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev 32:1073–1086

    Article  PubMed  CAS  Google Scholar 

  37. Weinstock M (2001) Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 65:427–451

    Article  PubMed  CAS  Google Scholar 

  38. Gotz AA, Stefanski V (2007) Psychosocial maternal stress during pregnancy affects serum corticosterone, blood immune parameters and anxiety behaviour in adult male rat offspring. Physiol Behav 90:108–115

    Article  PubMed  Google Scholar 

  39. Veenema AH (2012) Toward understanding how early-life social experiences alter oxytocin- and vasopressin-regulated social behaviors. Horm Behav 61:304–312

    Article  PubMed  CAS  Google Scholar 

  40. Storm EE, Tecott LH (2005) Social circuits: peptidergic regulation of mammalian social behavior. Neuron 47:483–486

    Article  PubMed  CAS  Google Scholar 

  41. Popik P, Vetulani J (1991) Opposite action of oxytocin and its peptide antagonists on social memory in rats. Neuropeptides 18:23–27

    Article  PubMed  CAS  Google Scholar 

  42. Popik P, Wolterink G, De Brabander H et al (1991) Neuropeptides related to [Arg8]vasopressin facilitates social recognition in rats. Physiol Behav 49:1031–1035

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from CNPq, FAPESP, FAPERGS and CAPES.

Conflict of interest

There was no conflict of interests.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Fisiologia, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Sarmento Leite, 500, Porto Alegre, RS, CEP 90050-170, Brazil

    Marcelo Alves de Souza, Pâmela Rossi Menegotto, Thiago Pereira Henriques & Aldo Bolten Lucion

  2. Programa de Pós-Graduação em Neurociências, Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Sarmento Leite, 500, Porto Alegre, RS, CEP 90050-170, Brazil

    Lígia Aline Centenaro & Matilde Achaval

  3. Departamento de Farmácia, Universidade Estadual do Centro-Oeste do Paraná, Simeão Camargo de Sá, 03, Guarapuava, PR, CEP 85040-080, Brazil

    Juliana Bonini

  4. Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Universitária, 2069, Cascavel, PR, CEP 85819-110, Brazil

    Marcelo Alves de Souza & Lígia Aline Centenaro

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  1. Marcelo Alves de Souza
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  2. Lígia Aline Centenaro
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Correspondence to Marcelo Alves de Souza.

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de Souza, M.A., Centenaro, L.A., Menegotto, P.R. et al. Prenatal Stress Produces Social Behavior Deficits and Alters the Number of Oxytocin and Vasopressin Neurons in Adult Rats. Neurochem Res 38, 1479–1489 (2013). https://doi.org/10.1007/s11064-013-1049-5

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  • DOI: https://doi.org/10.1007/s11064-013-1049-5

Keywords

  • Prenatal stress
  • Cross-fostering
  • Social memory
  • Social interaction
  • Oxytocin
  • Vasopressin