Skip to main content
SpringerLink
Log in

The effect of central noradrenergic system lesion on dopamine (DA) and serotonin (5-HT) synthesis rate following administration of 5-HT3 receptor ligands in chosen parts of the rat brain

  • Original research article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Introduction

Since little has been known about the effect of the central noradrenergic system on the reactivity of serotonin 5-HT3 receptors, the aim of the current study was to find out whether this reactivity could be altered by chemical damage to the system in adult rats in early developmental stage.

Materials and methods

Adult male Wistar rats with central noradrenergic lesion induced by DSP-4 on day 1 and 3 of life were injected with analgesic model substance – morphine, serotoninergic 5-HT3 receptor agonist (1-phenylbiguanide, PBG), 5-HT3 receptor antagonist (ondansetron) or both compounds jointly followed by decarboxylase inhibitor of aromatic amino acids (NSD-1050). After 30 min following NSD-1050 injection, the animals were decapitated using a guillotine. Chosen cerebral structures were dissected, and the contents of 5-hydroxytryptofan (5-HTP) and l-dihydroxyphenylalanine (l-DOPA) were determined using high-pressure liquid chromatography with electrochemical detection (HPLC/ED).

Results

Neither PBG nor morphine affected l-DOPA contents in the hippocampus in control rats; however, DSP-4 lesion caused a significant decrease in the synthesis rate of DA in this structure. Hippocampal contents of 5-HTP increased after morphine or PBG administration, and central noradrenergic lesion attenuated this effect. Morphine or PBG decreased cerebellar DA synthesis rate in control rats and DSP-4 lesion did not modify it. Cerebellar levels of 5-HTP increased after morphine or PBG challenge in control rats. DSP-4 lesion intensified the effect of morphine and attenuated that of PBG. Ondansetron abolished the effects mediated by PBG. We did not observe any impact of PBG or ondansetron on DA and 5-HT synthesis in the striatum.

Conclusion

Damage to the central noradrenergic system in rat newborns, through altered reactivity of central 5-HT3 receptors, results in permanent disorders in serotoninergic transmission in hippocampus and cerebellum as well as dopaminergic transmission in hippocampus, which may attenuate the activity of the descending pathways that derive from these structures.

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. Pertovaara A. Noradrenergic pain modulation. Prog Neurobiol 2006;80:53–83.

    Article  CAS  PubMed  Google Scholar 

  2. Schildkraut JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 1965;122:509–22.

    Article  CAS  PubMed  Google Scholar 

  3. Coppen A. The biochemistry of affective disorders. Br J Psychiatry 1967;113:1237–64.

    Article  CAS  PubMed  Google Scholar 

  4. Gray AM, Pache DM, Sewell RDE. Do alpha[sub 2]-adrenoceptors play a role in the antinociceptive mechanism of action of antidepressant compounds? Eur J Pharmacol 1999;378:161–8.

    Article  CAS  PubMed  Google Scholar 

  5. Otsuka N, Kiuchi Y, Yokogawa F, Masuda Y, Oguchi K, Hosoyamada A. Antinociceptive efficacy of antidepressants: assessment of five antidepressants and four monoamine receptors in rats. J Anesth 2001;15:154–8.

    Article  CAS  PubMed  Google Scholar 

  6. Stefański R, Płaźnik A, Nazar M, Jessa M. Neurofizjologiczne koncepcje powstawania lęku. Post Psychiatr Neurol 1994;3:1–12.

    Google Scholar 

  7. Strickland PL, Deakin JF, Percival C, Dixon J, Gater RA, Goldberg DP. Biosocial origins of depression in the community. Interactions between social adversity, cortisol and serotonin neurotransmission. Br J Psychiatry 2002;180:168–73.

    Article  PubMed  Google Scholar 

  8. Mann JJ, McBride PA, Brown RP, Linnoila M, Leon AC, DeMeo M. Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients. Arch Gen Psychiatry 1992;49:442–6.

    Article  CAS  PubMed  Google Scholar 

  9. Roggenbach J, Muller-Oerlinghausen B, Franke L, Uebelhack R, Blank S, Ahrens B. Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects. J Neural Transm 2007;114:479–87.

    Article  CAS  PubMed  Google Scholar 

  10. Wolkowitz OM, Epel ES, Reus V. Stress hormone-related psychopathology: pathophysiological and treatment implications. World J Biol Psychiatry 2001;2:115–43.

    Article  CAS  PubMed  Google Scholar 

  11. Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med 2001;7:541–7.

    Article  CAS  PubMed  Google Scholar 

  12. Quednow BB, Westheide J, Kuhn KU, Werner P, Maier W, Hawellek B, Wagner M. Normal prepulse inhibition and habituation of acoustic startle response in suicidal depressive patients without psychotic symptoms. J Affect Disord 2006;92:299–303.

    Article  PubMed  Google Scholar 

  13. Archer T, Jonsson G, Minor BG, Post C. Noradrenergic-serotoninergic interactions and nociception in the rat. Eur J Pharmacol 1986;120:295–307.

    Article  CAS  PubMed  Google Scholar 

  14. Jaim-Etcheverry G, Zieher LM. DSP-4 a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats. Brain Res 1980;188:513–23.

    Article  CAS  PubMed  Google Scholar 

  15. Kostrzewa RM, Kostrzewa JP, Brus R, Kostrzewa RA, Nowak P. Proposed animal model of severe Parkinson’s disease: neonatal 6-hydroksydopamine-lesion of dopaminergic innervation of striatum. J Neural Transm 2006;70:277–9.

    CAS  Google Scholar 

  16. Roczniak W, Wróbel J, Dolczak L, Nowak P. Influence of central noradrenergic system lesion on the serotoninergic 5-HT3 receptor mediated analgesia in rats. Adv Clin Exp Med 2013;22:629–38.

    PubMed  Google Scholar 

  17. Roczniak W. Assessment of dopamine (DA) synthesis rate in selected parts of the rat brain with central noradrenergic lesion after administration of 5-HT3 receptor ligands. Postepy Hig Med Dosw 2013;67:648–52.

    Article  Google Scholar 

  18. Roczniak W, Nowak P. Interaction between central noradrenergic system and serotoninergic 5-HT3 receptor mediated analgesia in rats. Adv Clin Exp Med 2010;3–4:7–17.

    Google Scholar 

  19. Hewlett WA, Fridman S, Trivedi BL, Schmidt DE, de Paulis T, Ebert MH. Characterization of desamino-5-[125I]iodo-3-methoxy-zacopride ([125I]MIZAC) binding to 5-HT3 receptors in the rat brain. Prog Neuropsy-chopharmacol Biol Psychiatry 1998;22:397–410.

    Article  CAS  Google Scholar 

  20. Nowak P, Labus Ł, Kostrzewa RM, Brus R. DSP-4 prevents dopamine receptor priming by quinpirole. Pharmacol Biochem Behav 2006;84:3–7.

    Article  CAS  PubMed  Google Scholar 

  21. Brus R, Nowak P, Labus Ł, Bortel A, Dąbrowska J, Kostrzewa RM. Neonatal lesion of noradrenergic neurons in rat brain: interaction with the dopaminergic system. Pol J Pharmacol 2004;56:232.

    Google Scholar 

  22. Dąbrowska J, Nowak P, Brus R. Desensitization of 5-HT (1A) autoreceptors induced by neonatal DSP-4 treatment. Eur Neuropharmacol 2007;17:129–37.

    Article  Google Scholar 

  23. Nowak P, Noras Ł, Jochem J, Szkilnik R, Brus H, Kőrössy È, et al. Histaminergic activity in a rodent model of Parkinson’s disease. Neurotox Res 2009;15:246–51.

    Article  CAS  PubMed  Google Scholar 

  24. Baumgarten HG, Björklaund A, Lachenmayer L, Nobin A. Evaluation of the effects of 5,7-dihydroxytryptamine on serotonin and catecholamine neurons in the rat CNS. Acta Physiol Scand Suppl 1973;391:1–19.

    CAS  PubMed  Google Scholar 

  25. Bortel A, Nowak P, Brus R. Neonatal DSP-4 treatment modifies GABAergic neurotransmission in the prefrontal cortex of adult rats. Neurotox Res 2008;13:247–52.

    Article  CAS  PubMed  Google Scholar 

  26. Bortel A, Nitka D, Słomian L, Nowak P, Brus R, Kőrössy È, et al. Neonatal noradrenergic lesion with DSP-4 modifies the convulsant effect of bicuculine and pentylenetetrazole in adult rats. Behavioral and biochemical studies. Ann Acad Med Siles 2008;62:46–52.

    Google Scholar 

  27. Johnston CA, Moore KE. The effect of morphine on 5-hydroxytryptamine synthesis and metabolism in the striatum, and several discrete hypothalamic regions of the rat brain. J Neural Transm 1983;57:65–73.

    Article  CAS  PubMed  Google Scholar 

  28. Courade JP, Caussade F, Maritn K, Besse D, Delchambre C, Hanoun N, et al. Effects of acetaminophen on monoaminergic systems in the rat central nervous system. Naunyn Schmiedebergs Arch Pharmacol 2001;364:534–7.

    Article  CAS  PubMed  Google Scholar 

  29. Sastre-Coll A, Esteban S, García-Sevilla JA. Supersensitivity of 5-HT1A autoreceptors and alpha2-adrenoceptors regulating monoamine synthesis in the brain of morphine-dependent rats. Naunyn Schmiedebergs Arch Pharmacol 2002;365(March (3)):210–9.

    Article  CAS  PubMed  Google Scholar 

  30. Rossetti ZL, Longu G, Mercuro G, Gessa GL. Extraneuronal noradrenaline in the prefrontal cortex of morphine-dependent rats: tolerance and withdrawal mechanisms. Brain Res 1993;609:316–20.

    Article  CAS  PubMed  Google Scholar 

  31. Tao R, Auerbach SB. Increased extracellular serotonin in rat brain after systemic or intraraphe administration of morphine. J Neurochem 1994;63(August (2)):517–24.

    Article  CAS  PubMed  Google Scholar 

  32. Wang QP, Ochiai H, Nakai Y. GABAergic innervation of serotonergic neurons in the dorsal raphe nucleus of the rat: studies by electron microscopy and double immunostaining. Brain Res Bull 1992;29:943–8.

    Article  CAS  PubMed  Google Scholar 

  33. Johnson SW, North R. Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 1992;12:483–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dąbrowska J, Nowak P, Brus R. Reactivity of 5-HT1A receptor in adult rats after neonatal noradrenergic neurons’ lesion – implications for antidepressant-like action. Brain Res 2008;1239(November 6):66–76.

    Article  PubMed  Google Scholar 

  35. Bortel A, Słomian L, Nitka D, Swierszcz M, Jaksz M, Adamus-Sitkiewicz B, et al. Neonatal N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) treatment modifies the vulnerability to phenobarbital- and ethanol-evoked sedative-hypnotic effects in adult rats. Pharmacol Rep 2008;60(May–June (3)):331–8.

    CAS  PubMed  Google Scholar 

  36. Mongeau R, De Montigny C, Blier P. Activation of 5-HT3 receptors enhances the electrically evoked release of [3H] noradrenaline in rat brain limbic structures. Eur J Pharmacol 1994;256:269–79.

    Article  CAS  PubMed  Google Scholar 

  37. Santiago M, Machado A, Cano J. 5-HT3 receptor agonist induced carrier-mediated release of dopamine in rat striatum in vivo. Br J Pharmacol 1995;116:1545–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Blier P, Bouchard C. Functional characterization of a 5-HT3 receptor which modulates the release of 5-HT in the guinea-pig brain. Br J Pharmacol 1993;108:13–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Elverfors A, Nissbrandt H. Effects of D-amphetamine on dopaminergic neurotransmission; a comparison between the substantia nigra and the striatum. Neuropharmacology 1992;31:661–70.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Dr. Janusz Daab Hospital of Trauma Surgery in Piekary Śląskie, Poland

    Wojciech Roczniak & Wojciech Widuchowski

  2. The Jan Grodek Higher Vocational State School in Sanok, Medical Institute, Poland

    Magdalena Babuśka-Roczniak & Elżbieta Cipora

  3. Department of Environmental Health and Epidemiology, Institute of Occupational Medicine in Sosnowiec, Poland

    Jerzy Kwapuliński

  4. Silesian Medical University of Katowice, Faculty of Pharmacy in Sosnowiec, Poland

    Barbara Brodziak-Dopierała

  5. Department of Toxicology and Health Protection, Medical University of Silesia, Katowice, Poland

    Przemysław Nowak

  6. Department of Pediatrics in Zabrze, Medical University of Silesia in Katowice, Poland

    Joanna M. Oświęcimska

Authors
  1. Wojciech Roczniak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Magdalena Babuśka-Roczniak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jerzy Kwapuliński
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Barbara Brodziak-Dopierała
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wojciech Widuchowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elżbieta Cipora
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Przemysław Nowak
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Joanna M. Oświęcimska
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wojciech Roczniak.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Roczniak, W., Babuśka-Roczniak, M., Kwapuliński, J. et al. The effect of central noradrenergic system lesion on dopamine (DA) and serotonin (5-HT) synthesis rate following administration of 5-HT3 receptor ligands in chosen parts of the rat brain. Pharmacol. Rep 67, 146–151 (2015). https://doi.org/10.1016/j.pharep.2014.08.018

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2014.08.018

Keywords

Search

Navigation