Skip to main content
SpringerLink
Log in

Effects of neonatal handling on behavior and the stress response in rats selected for their reaction towards humans

  • Published:
Russian Journal of Genetics: Applied Research

Abstract

It is known that neonatal handling may cause long-term changes in neurobiological and behavioral phenotypes. The neonatal handling of rats selected for enhanced aggressiveness towards humans (“aggressive” rats of generation 44) significantly mitigates aggression and stress responsiveness. However, the levels of corticosterone in stress in intact aggressive rats of later (70s) generations are lower than in generation 44, which differ little from the corresponding value in “tame” rats, selected in the opposite direction, for the absence of the aggressiveness towards humans. The goal of the present study is to find out whether the decrease in the stress response in aggressive rats at the current stage of selection is accompanied by a decrease in the influence of handling on aggressiveness. Experiments have been conducted with the Norway rat populations of the 75th generation of selection for aggressive and tame behavior, respectively. It has been found that the neonatal handling of aggressive animals causes a significant decrease in aggressiveness, albeit, considerably smaller than in generation 44. In both aggressive and tame rats, the blood corticosterone level under stress returns to the basal level for a longer time than in the corresponding control groups. Neonatal handling decreases the amount of mRNA for the glucocorticoid receptor (GR) in the hippocampus of aggressive rats but does not significantly affect the amount of mRNA for the corticotropin-releasing hormone (CRH) in the hypothalamus. However, in the control groups the level of CRH mRNA recorded in aggressive rats is higher than in tame ones. On the contrary, no differences in the GR mRNA are found between the strains, in contrast to earlier generations. It has been shown that the neonatal handling of pups is beneficial for maternal behavior in tame rats. Thus, the results obtained in generation 75 of selection indicate that the effect of handling on aggressiveness weakens with decreasing stress responsiveness in aggressive rats. This is likely to be related to the changing amount of GR in the hippocampus and stronger glucocorticoid-mediated feedback at the current stage of selection. The minor prolongation of the stress response appears to be related to the stressing component of neonatal handling rather than to changes in maternal care.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

  • Bagot, R.C. and Meaney, M.J., Epigenetics and the biological basis of gene x environment interactions, J. Am. Acad. Child Adolesc. Psychiatry, 2010, vol. 49, no. 8, pp. 752–771. doi 10.1016/j.jaac.2010.06.001

    Article  PubMed  Google Scholar 

  • Bale, T.L., Epigenetic and transgenerational reprogramming of brain development, Nat. Rev. Neurosci., 2015, vol. 16, pp. 332–344. doi 10.1038/nrn3818

    Article  CAS  PubMed  Google Scholar 

  • Belyaev, D.K. and Borodin, P.M., Vliyanie stressa na nasledstvennuyu izmenchivost’ i ego rol’ v evolyutsii. Evolyutsionnaya genetika (The Impact of Stress on the Genetic Variability and Its Role in Evolution. Evolution Genetics), Leningrad: LGU, 1982.

    Google Scholar 

  • Blank, T. and Spiess, J., Corticotropin-releasing factor (CRF) and CRF-related peptides–a linkage between stress and anxiety, in Stress–From Molecules to Behavior: A Comprehensive Analysis of the Neurobiology of Stress Responses, Weinheim: Wiley-VCH, 2010, pp. 151–165.

    Google Scholar 

  • Dygalo, N.N., Shishkina, G.T., Borodin, P.M., and Naumenko, E.V., The role of neurochemical systems of the brain in the change in the reactivity of the pituitary-adrenal complex of gray rat selected for behavior, Zh. Evol. Biokhim. Fiziol., 1985, vol. 21, no. 4, pp. 342–347.

    CAS  PubMed  Google Scholar 

  • Francis, D.D., Diorio, J., Plotsky, P.M., and Meaney, M.J., Environmental enrichment reverses the effects of maternal separation on stress reactivity, J. Neurosci., 2002, vol. 22, no. 18, pp. 7840–7843.

    CAS  PubMed  Google Scholar 

  • Gariépy, J.-L., Rodriguiz, R.M., and Jones, B.C., Handling, genetic and housing effects on the mouse stress system, dopamine function, and behavior, Pharmacol. Biochem. Behav., 2002, vol. 73, no. 1, pp. 7–17. doi 10.1016/S0091-3057(02)00789-X

    Article  PubMed  Google Scholar 

  • Gerbek, Yu.E., Os’kina, I.N., Gulevich, R.G., and Plyusnina, I.Z., Influence of maternal methyl-rich diet on glucocorticoid receptor gene expression in the hippocampus of rats selected for behavior, Tsitol. Genet., 2010, vol. 44, no. 2, pp. 45–52.

    CAS  PubMed  Google Scholar 

  • Gonzalez-Liencres, C., Shamay-Tsoory, S.G., and Brüne, M., Towards a neuroscience of empathy: Ontogeny, phylogeny, brain mechanisms, context and psychopathology, Neurosci. Biobehav. Rev., 2013, vol. 37, no. 8, pp. 1537–1548. doi 10.1016/j.neubiorev.2013.05.001

    Article  PubMed  Google Scholar 

  • Herbeck, Y.E., Os’kina, I.N., Gulevich, R.G., and Plyusnina, I.Z., Effects of maternal methyl-supplement diet on hippocampal glucocorticoid receptor mRNA expression in rats selected for behavior, Cytol. Genet., 2010, vol. 44, no. 2, pp. 108–113. doi 10.3103/S0095452710020064

    Article  Google Scholar 

  • Konoshenko, M.Y. and Plyusnina, I.Z., Behavioral effects of bidirectional selection for behavior towards human in virgin and lactate Norway rats, Behav. Processes, 2012, vol. 90, no. 2, pp. 180–188.

    Article  PubMed  Google Scholar 

  • Kosten, T.A., Lee, H.J., and Kim, J.J., Early life stress impairs fear conditioning in adult male and female rats, Brain Res., 2006, vol. 1087, pp. 142–150. doi 10.1016/j.brainres.2006.03.009

    Article  CAS  PubMed  Google Scholar 

  • Levine, S., Maternal and environmental influences on the adrenocortical response to stress in weanling rats, Science, 1967, vol. 156, pp. 258–260.

    Article  CAS  PubMed  Google Scholar 

  • Liu, D., Diorio, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., Sharma, S., Pearson, D., Plotsky, P.M., and Meaney, M.J., Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitaryadrenal responses to stress, Science, 1997, vol. 277, no. 5332, pp. 1659–1662.

    Article  CAS  PubMed  Google Scholar 

  • Macri, S., Mason, G.J., and Wu, H., Dissociation in the effects of neonatal maternal separations on maternal care and the offspring’s HPA and fear responses in rats, Eur. J. Neurosci., 2004, vol. 20, no. 4, pp. 1017–1024. doi 10.1111/j.1460-9568.2004.03541.x

    Article  PubMed  Google Scholar 

  • Marini, F., Pozzato, C., Andreetta, V., Jansson, B., Arban, R., Domenici, E., and Carboni, L., Single exposure to social defeat increases corticotropinreleasing factor and glucocorticoid receptor mRNA expression in rat hippocampus, Brain Res., 2006, vol. 1067, pp. 25–35. doi 10.1016/j.brainres. 2005.10.002

    Article  CAS  PubMed  Google Scholar 

  • McEwen, B.S., Allostasis and allostatic load: Implications for neuropsychopharmacology, Neuropsychopharmacology, 2000, vol. 22, no. 2, pp. 108–124.

    Article  CAS  PubMed  Google Scholar 

  • Murphy, B.E., Some studies of the protein binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay, J. Clin. Endocrinol. Metab., 1967, vol. 27, pp. 973–990.

    Article  CAS  PubMed  Google Scholar 

  • Os’kina, I.N., Gerbek, Yu.E., Shikhevich, S.G., Plyusnina, I.Z., and Gulevich, R.G., Changes in the hypothalamic- pituitary-adrenal system in the selection of animals for domestic behavior, Inf. Vestn. Vavilovskogo O-va Genet. Sel., 2008, vol. 12, no. 1, pp. 2–39.

    Google Scholar 

  • Os’kina, I.N. and Plyusnina, I.Z., The pituitary-adrenal system in wild gray rats selected for domestic behavior and neonatal handling, Materialy nauch. konf. “Endokrinnye mekhanizmy regulyatsii funktsii v norme i patologii” (Proc. Sci. Conf. Endocrine Mechanisms of Regulation of Functions in Health and Disease), Novosibirsk, 1997, pp. 114–115.

    Google Scholar 

  • Peinnequin, A., Mouret, C., Birot, O., Alonso, A., Mathieu, J., Clarençon, D., Agay, D., Chancerelle, Y., and Multon, E., Rat pro-inflammatory cytokine and cytokine related mRNA quantification by real-time polymerase chain reaction using SYBR green, BMC Immunol., 2004, vol. 5, p. 3. doi 10.1186/1471-2172-5-3

    Article  PubMed  PubMed Central  Google Scholar 

  • Plyusnina, I. and Oskina, I., Behavioral and adrenocortical responses to open-field test in rats selected for reduced aggressiveness toward humans, Physiol. Behav., 1997, vol. 61, no. 3, pp. 381–385.

    Article  CAS  PubMed  Google Scholar 

  • Plyusnina, I.Z., Oskina, I.N., Tibeikina, M.A., and Popova, N.K., Cross-fostering effects on weight, exploratory activity, acoustic startle reflex and corticosterone stress response in Norway gray rats selected for elimination and for enhancement of aggressiveness towards human, Behav. Genet., 2009, vol. 39, no. 2, pp. 202–212. doi 10.1007/s10519-008-9248-6

    Article  PubMed  Google Scholar 

  • Plyusnina, I.Z., Tarantsev, I.G., Bulushev, E.D., Konoshenko, M.Yu., Kozhemyakina, R.V., Gerbek, Yu.E., and Os’kina, I.N., Analysis of maternal behavior in hand and aggressive gray rats, Zh. Vyssh. Nervn. Deyat. im. I. P. Pavlova, 2013, vol. 63, no. 3, pp. 375–383. doi 10.1007/s11055- 014-9993-3

    Google Scholar 

  • Plyusnina, I.Z., Tarantsev, I.G., Bulushev, E.D., Konoshenko, M.Y., Kozhemyakina, R.V., Gerbek, Y.E., and Os’kina, I.N., Analysis of maternal behavior in tame and aggressive gray rats, Neurosci. Behav. Physiol., 2014, vol. 44, no. 8, pp. 856–862. doi 10.1007/s11055-014-9993-3

    Article  Google Scholar 

  • Prasolova, L.A., Gerbek, Yu.E., Gulevich, R.G., Shikhevich, S.G., Konoshenko, M.Yu., Kozhemyakina, R.V., Os’kina, I.N., and Plyusnina, I.Z., The effects of prolonged selection for behavior on the stress response and activity of the reproductive system of male grey mice (Rattus norvegicus), Russ. J. Genet., 2014, vol. 50, no. 8, pp. 846–852.

    Article  CAS  Google Scholar 

  • Steimer, T., Escorihuela, R.M., Fernández-Teruel, A., and Driscoll, A.P., Long-term behavioural and neuroendocrine changes in Roman high-(RHA/Verh) and low-(RLA-Verh) avoidance rats following neonatal handling, Int. J. Dev. Neurosci., 1998, vol. 16, no. 3, pp. 4–165. doi 10.1016/S0736-5748(98)00032-X

    Google Scholar 

  • Tang, A.C., Akers, K.G., Reeb, B.C., Romeo, R.D., and McEwen, B.S., Programming social, cognitive, and neuroendocrine development by early exposure to novelty, Proc. Natl. Acad. Sci. U.S.A., 2006, vol. 103, pp. 15716–15721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang, A.C., Reeb-Sutherland, B.C., Romeo, R.D., and McEwen, B.S., On the causes of early life experience effects: Evaluating the role of mom, Front. Neuroendocrinol., 2014, vol. 35, no. 2, pp. 245–251. doi 10.1016/j.yfrne.2013.11.002

    Article  PubMed  Google Scholar 

  • Tinnikov, A.A. and Bazhan, N.M., Determination of glucocorticoids in the blood plasma and adrenal incubates by competitive binding of hormones using protein without pre-extraction, Lab. Delo, 1984, vol. 12, pp. 709–713.

    Google Scholar 

  • Todeschin, A.S., Winkelmann-Duarte, E.C., Jacob, M.H., Aranda, B.C., Jacobs, S., Fernandes, M.C., Ribeiro, M.F., Sanvitto, G.L., and Lucion, A.B., Effects of neonatal handling on social memory, social interaction, and number of oxytocin and vasopressin neurons in rats, Horm. Behav., 2009, vol. 56, no. 1, pp. 93–100. doi 10.1016/ j.yhbeh.2009.03.006

    Article  CAS  PubMed  Google Scholar 

  • Veenema, A.H., Torner, L., Blume, A., Beiderbeck, D.I., and Neumann, I.D., Low inborn anxiety correlates with high intermale aggression: Link to ACTH response and neuronal activation of the hypothalamic paraventricular nucleus, Horm. Behav., 2007, vol. 51, no. 1, pp. 11–19. doi 10.1016/j.yhbeh.2006.07.004

    Article  CAS  PubMed  Google Scholar 

  • Veenema, A.H., Toward understanding how early-life social experiences alter oxytocin- and vasopressin-regulated social behaviors, Horm. Behav., 2012, vol. 61, no. 3, pp. 304–312. doi 10.1016/j.yhbeh.2011.12.002

    Article  CAS  PubMed  Google Scholar 

  • Weaver, I.C., Cervoni, N., Champagne, F.A., D’Alessio, A.C., Sharma, S., Seckl, J.R., Dymov, S., Szyf, M., and Meaney, M.J., Epigenetic programming by maternal behavior, Nat. Neurosci., 2004, vol. 7, no. 8, pp. 847–854. doi 10.1038/nn1276

    Article  CAS  PubMed  Google Scholar 

  • Zhang, T.Y., Labonté, B., Wen, X.L., Turecki, G., and Meaney, M.J., Epigenetic mechanisms for the early environmental regulation of hippocampal glucocorticoid receptor gene expression in rodents and humans, Neuropsychopharmacology, 2013, vol. 38, pp. 111–123. doi 10.1038/npp.2012.149

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia

    Yu. E. Herbeck, O. A. Amelkina, M. Yu. Konoshenko, S. G. Shikhevich, R. G. Gulevich, R. V. Kozhemyakina, I. Z. Plyusnina & I. N. Oskina

  2. Novosibirsk State University, Novosibirsk, Russia

    O. A. Amelkina

  3. Leibniz Institute for Zoo and Wildlife Research, Department of Reproduction Biology, Berlin, Germany

    O. A. Amelkina

Authors
  1. Yu. E. Herbeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. A. Amelkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Yu. Konoshenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. G. Shikhevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. G. Gulevich
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. V. Kozhemyakina
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I. Z. Plyusnina
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. I. N. Oskina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu. E. Herbeck.

Additional information

Original Russian Text © Yu.E. Herbeck, O.A. Amelkina, M.Yu. Konoshenko, S.G. Shikhevich, R.G. Gulevich, R.V. Kozhemyakina, I.Z. Plyusnina, I.N. Oskina, 2016, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2016, Vol. 20, No. 2, pp. 145–154.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Herbeck, Y.E., Amelkina, O.A., Konoshenko, M.Y. et al. Effects of neonatal handling on behavior and the stress response in rats selected for their reaction towards humans. Russ J Genet Appl Res 7, 71–81 (2017). https://doi.org/10.1134/S2079059717010051

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079059717010051

Keywords

Search

Navigation