Skip to main content
Log in

Effects of Decrease of Serotonin Synthesis and Subsequent Stress in Embryogenesis on Rat Pain Sensitivity during the Prepuberty Period of Development

  • Comparative and Ontogenic Physiology
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

In the 25-day old rats there were studied effects of prenatal serotonin (5-HT) depletions and stress on pain sensitivity evaluated using formalin test by indexes of the biphasic behavioral response (BBR)-the number of flexions and shakings as well as duration of licking of the formalin injected leg, duration of the first and second response phases and on morphofunctional characteristics of the brain structures involved in BBR. The 5-HT depletion (a single intraperitoneal injection of parachlorophenylalanine, an inhibitor of 5-HT synthesis, to pregnant females at the initial period of development of the serotoninergic system) produced morphological lesions in the neocortex areas and hippocampus and raphe nuclei, which were accompanied by an essential decrease of the pain sensitivity (until its complete inhibition) during the second, tonic, BBR phase. In the prenatally stressed rats (immobilization of pregnant females for the last pregnancy week) with prenatal 5-HT depletion the nerve cell death in the above brain structures was accompanied by an increase of the pain sensitivity revealed by all response indexes during the second, tonic phase, whereas in the prenatally stressed rats developed without the intervention into the serotoninergic system, only one index was found to increase. The obtained results indicate that 5-HT participates in formation of the tonic nociceptive system and in mediation of effects of the prenatal stress on the pain sensitivity to the long-term nociceptive stimulus.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. Naumenko, E.V., Dygalo, N.N., and Maslova, L.N., The Long-Term Modification of the Stress Reactivity by Actions in Prenatal Ontogenesis, Ontogeneticheskie i genetiko-evolyutsionnye aspekty neiroendokrinnoi regulyatsii stressa (Ontogenetic and Genetic-Evolutional Aspects of the Neuroendocrine Stress Regulation), Naumenko, E.V. and Popova, N.K., Eds., Novosibirsk, 1990, pp. 40–55.

  2. Kassil’, V.G., Otellin, V.A., Khozhai, L.I., and Kostkin, V.B., Critical Periods of Brain Development, Sechenov Ross. Fiziol. Zh., 2000, vol. 86, pp. 1418–1425.

    CAS  Google Scholar 

  3. Shalyapina, V.G., Zaichenko, I.N., Ordyan, N.E., and Batuev, A.S., Change of the Neuroendocrine Regulation of the Rat Adaptive Behavior after Stress in Late Prenatal Ontogenesis, Sechenov Ross. Fiziol. Zh., 2001, vol. 87, pp. 1193–1201.

    CAS  Google Scholar 

  4. Otellin, V.A. and Khozhai, L.I., The Role of Serotonin in Prenatal Brain Development and Its Pathology in Mammals, Teoreticheskie i prikladnye aspekty embrional’nogo ontogeneza (Theoretical and Applied Aspects of Embryonic Ontogenesis), St. Petersburg, 2002, pp. 25–32.

  5. Weinstock, M., Alterations Induced by Gestational Stress in Brain Morphology and Behaviour of the Offspring, Progr. Neurobiol., 2001, vol. 65, pp. 427–451.

    Article  CAS  PubMed  Google Scholar 

  6. Kofman, O., The Role of Prenatal Stress in the Etiology of Developmental Behavioural Disorders, Neurosci. Biobehav. Rev., 2002, vol. 26, pp. 457–470.

    Article  CAS  PubMed  Google Scholar 

  7. Rode, V., Okava, T., Shtal, F., Getz, F., Tenies, R., Takeshita, S., Arakava, S., Kambegava, A., Arai, K., Okinaga, S., and Derner, G., The Variations of the Neuroendocrine System in Rat Fetus by Acute Stress at the End of Pregnancy, Ontogeneticheskie i genetiko-evolyutsionnye aspekty neiroendokrinnoi regulyatsii stressa (Ontogenetic and Genetic-Evolutional Aspects of the Neuroendocrine Stress Regulation), Naumenko, E.V. and Popova, N.K., Eds., Novosibirsk, 1990, pp. 40–55.

  8. Reznikov, A.G., Kosenko, N.D., and Tarasenko, L.V., Participation of Endogenous Opioids in Pathogenesis of Early Neuroendocrine Manifestations of the Prenatal Stress Syndrome, Byull. Exper. Biol. Med., 2003, vol. 135, pp. 497–499.

    Google Scholar 

  9. Wadhwa, P.D., Sandman, C.A., and Garite, T.J., The Neurobiology of Stress in Human Pregnancy: Implications for Prematurity and Development of the Fetal Nervous System, Progr. Brain Res., 2001, vol. 133, pp. 131–142.

    CAS  Google Scholar 

  10. Aleksandrov, A.A., Polyakova, O.I., and Batuev, A.S., Effect of the Prenatal Stress on the Rat Leaning in Morris Test, Sechenov Ross. Fiziol. Zh., 1999, vol. 85, pp. 1031–1034.

    CAS  Google Scholar 

  11. Butkevich, I.P. and Vershinina, E.A., Prenatal Stress Alters Time Characteristics and Intensity of Formalin-Induced Pain Responses in Juvenile Rats, Brain Res., 2001, vol. 915, pp. 88–93.

    Article  CAS  PubMed  Google Scholar 

  12. Chaouloff, F., Serotonin, Stress and Corticoids, J. Psychopharmacol., 2000, vol. 14, pp. 419–421.

    Google Scholar 

  13. Lauder, J.M. and Krebs, H., Effects of p-Chlorophenylalanine on Time of Neuronal Origin during Embryogenesis in the Rat, Brain Res., 1976, vol. 107, pp. 638–644.

    Article  CAS  PubMed  Google Scholar 

  14. Lauder, J.M., Ontogeny of the Serotonergic System in the Rat: Serotonin as a Developmental Signal, Ann. N.Y. Acad. Sci., 1990, vol. 600, pp. 297–313.

    CAS  PubMed  Google Scholar 

  15. Babichev, V.N., Neiroendokrinologiya pola (Neuroendocrinology of Gender), Moscow, 1981.

  16. Green, G.M., Scarth, J., and Dickenson, A., An Excitatory Role for 5-HT in Spinal Inflammatory Nociceptive Transmission; State-Dependent Actions via Dorsal Horn 5-HT3 Receptors in the Anaesthetized Rat, Pain, 2000, vol. 89, pp. 81–88.

    Article  CAS  PubMed  Google Scholar 

  17. Dubuisson, D. and Dennis, S.G., The Formalin Test: a Quantitative Study of the Analgesic Effects of Morphine, Meperidine, and Brain Stimulation in Rats and Cats, Pain, 1977, vol.4, pp. 161–174.

    Article  CAS  PubMed  Google Scholar 

  18. Butkevich, I.P., Mikhailenko, V.A., Khozhai, L.I., and Otellin, V.A., Prenatal Serotonin Depletion Changes Behavioral Response in the Formalin Nociceptive Test in Rat, Dokl. RAN, 2003, vol. 390, pp. 562–564.

    Google Scholar 

  19. Barr, G.A., Maturation of the Biphasic Behavioral and Heart Rate Response in the Formalin Test, Pharm. Biochem. Behav., 1998, vol. 60, pp. 329–335.

    Article  CAS  Google Scholar 

  20. Azmitia, E.C. and Segal, M., An Autoradiographic Analysis of the Differential Ascending Projections of the Dorsal and Median Raphe Nuclei in the Rat, J. Comp. Neurol., 1978, vol. 179, pp. 641–659.

    Article  CAS  PubMed  Google Scholar 

  21. Verney, C., Lebrand, G., and Gaspar, P., Changing Distribution of Monoaminergic Markers in the Developing Human Cerebral Cortex with Special Emphasis on the Serotonin Transporter, Anat. Rec., 2002, vol. 267, pp. 87–93.

    Article  PubMed  Google Scholar 

  22. Morrow, T.J., Paulson, P.E., Dannemann, P.J., and Casey, K.L., Regional Changes in Forebrain Activation during the Early and Late Phase of Formalin Nociception: Analysis Using Cerebral Blood Flow in the Rat, Pain, 1988, vol. 75, pp. 355–365.

    Article  Google Scholar 

  23. Basbaum, A.I., Distinct Neurochemical Features of Acute and Persistent Pain, Proc. Natl Acad. Sci. USA, 1999, vol. 96, pp. 7739–7743.

    Article  CAS  PubMed  Google Scholar 

  24. Gebhart, F.F., Modulatory Effects of Descending Systems on Spinal Dorsal Horn Neurons, Spinal Afferent Processing, Yaksh, T.L., Ed., New York: Plenum, 1986, pp. 391–416.

    Google Scholar 

  25. Ren, K. and Dubner, R., Descending Modulation in Persistent Pain: An Update, Pain, 2002, vol. 100, pp. 1–6.

    Article  PubMed  Google Scholar 

  26. Lauder, J.M., Liu, J., and Grayson, D.R., In utero Exposure to Serotonergic Drugs Alters Neonatal Expression of 5-HT1A Receptor Transcripts: a Quantitative RT-PCR Study, Int. J. Dev. Neurosci., 2000, vol. 18, pp. 171–176.

    Article  CAS  PubMed  Google Scholar 

  27. Bell, J., Zhang, X., and Whitaker-Azmitia, P.M., 5-HT3 Receptor-Active Drugs Alter Development of Spinal Serotonergic Innervation: Lack of Effect of Other Serotonergic Agents, Brain Res., 1992, vol. 571, pp. 293–297.

    Article  CAS  PubMed  Google Scholar 

  28. Weidenfeld, J., Feldman, S., Itzik, A., van de Kar, L., and Newman, M.E., Evidence for a Mutual Interaction between Noradrenergic and Serotonergic Agonists in Stimulation of ACTH and Corticosterone Secretion in the Rat, Brain Res., 2002, vol. 941, pp. 113–117.

    Article  CAS  PubMed  Google Scholar 

  29. Peters, D.A., Prenatal Stress: Effects on Brain Biogenic Amine and Plasma Corticosterone Levels, Pharmacol. Biochem. Behav., 1982, vol. 17, no.4, pp. 721–725.

    Article  CAS  PubMed  Google Scholar 

  30. Naumenko, E.V., Tsentral’naya regulyatsiya gipofizarno-nadpochechnikovogo kompleksa (Central Regulaton of the Pituitary-Adrenal Complex), Leningrad, 1971.

Download references

Author information

Authors and Affiliations

Authors

Additional information

__________

Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 41, No. 2, 2005, pp. 168–175.

Original Russian Text Copyright © 2005 by Butkevich, Mikhailenko, Khozhai, Otellin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Butkevich, I.P., Mikhailenko, V.A., Khozhai, L.I. et al. Effects of Decrease of Serotonin Synthesis and Subsequent Stress in Embryogenesis on Rat Pain Sensitivity during the Prepuberty Period of Development. J Evol Biochem Phys 41, 211–220 (2005). https://doi.org/10.1007/s10893-005-0056-9

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10893-005-0056-9

Keywords

Navigation