Skip to main content
SpringerLink
Log in

Mesaton (phenylephrine) Potentiates the Antidepressant and Eliminates the Sedative Action of Amitriptyline in Rats

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Single i.m. doses of amitriptyline (10–30 mg/kg) induced a mild antidepressant effect in rats, decreasing immobility in the Porsolt test by factors of no more than 1.3–1.7. These doses of amitriptyline had significant sedative effects, as they decreased horizontal activity in the open field by factors of 3–6 and reduced vertical activity by factors of 2–2.5. Combined single i.m. administration of a low dose of amitriptyline (3 mg/kg) or a high dose of amitriptyline (30 mg/kg) combined with Mesaton (phenylephrine) at a threshold dose of 0.02 mg/kg (ineffective when given alone), induced a maximum antidepressant effect, decreasing immobility in the Porsolt test by factors of 3 and 4.6 respectively, but had no sedative side effect in the open field. The mechanism of potentiation of the antidepressant effect and elimination of the sedative effect of amitriptyline appears to be based on stimulation of gastric mucosal afferents by Mesaton.

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. E. G. Kostyukova, G. M. Granenov, L. A. Andreichuk, et al., Zh. Nevrol. Psikhiat., 103, No. 1, 24–29 (2003).

    Google Scholar 

  2. S. E. Serdyuk and V. E. Gmiro, “Adrenaline potentiates the analgesic and antidepressant actions of amitriptyline by stimulating gastric mucosal afferents,” Byull. Eksperim. Biol. Med., 144, No. 11, 535–537 (2007).

    Google Scholar 

  3. S. E. Serdyuk and V. E. Gmiro, “The analgesic and antidepressant actions of adrenaline stress in endogenous activation of the afferent systems of the stomach in rats,” Ros. Fiziol. Zh., 83, No. 8, 111–120 (1997).

    CAS  Google Scholar 

  4. S. E. Serdyuk and V. E. Gmiro, “The involvement of gastric afferents in the refl ex mechanisms of rapid adaptation of the stressors,” Fiziol. Zh. SSSR, 81, No. 9, 40–51 (1995).

    Google Scholar 

  5. S. E. Serdyuk and V. E. Gmiro, “Peripherally acting mediators of pain and analgesia potentiate the central analgesic action of fentanyl and Analgin in rats,” Ros. Fiziol. Zh., 98, No. 3, 325–330 (2012).

    CAS  Google Scholar 

  6. O. I. Epshtein, G. M. Molodavkin, T. A. Voronina, and S. A. Sergeeva, “The antidepressant properties of Proproten and amitriptyline: a comparative experimental study,” Byull. Eksperim. Biol. Med., 135, Suppl. No. 1, 34–36 (2003).

    Article  Google Scholar 

  7. G. Aston-Jones, B. Astier, and M. Ennis, “Inhibition of noradrenergic locus coeruleus neurons by C1 adrenergic cells in the rostral ventral medulla,” Neuroscience, 48, No. 2, 371–381 (1992).

    Article  CAS  PubMed  Google Scholar 

  8. M. Elamm T. H. Svensson, and P. Thoren, “Differentiated cardiovascular afferent regulation of locus coeruleus neurons and sympathetic nerves,” Brain. Res., 358, No. 1–2, 77–84 (1985).

    Article  Google Scholar 

  9. E. A. Engleman and D. T. Wong, “Regulation of extracellular concentrations of norepinephrine in hypothalamus of the conscious rat: effect of amitriptyline,” Chin. Physiol., 39, No. 1, 9–13 (1996).

    CAS  Google Scholar 

  10. T. A. Furukawa, H. McGuire, and C. Barbui, “Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review,” Brit. Med. J., 325, No. 7371, 991 (2002).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. R. D. Gibbons, K. Hur, D. K. Bhaumik, and J. J. Mann, “The relationship between antidepressant medication use and rate of suicide,” Arch. Gen. Psychiatry, 62, No. 2, 165–172 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. L. Grandoso, J. Pineda, and L. Ugedo, “Comparative study of the effects of desipramine and reboxetine on locus coeruleus neurons in rat brain slices,” Neuropharmacology, 46, No. 6, 815–823 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. M. M. Grant and J. M. Weiss, “Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity,” Biol. Psychiatry, 49, No. 2, 117–129 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. H. Hindmarch, “The behavioural toxicity of antidepressants: effects on cognition and sexual function,” Int. Clin. Psychopharmacol., 13, Suppl. 6, S5–S8 (1998).

    Article  PubMed  Google Scholar 

  15. S. T. Kaehler, A. Philippu, and N. Singewald, “Effects of local MAO inhibition in the locus coeruleus on extracellular serotonin and 5-HIAA during exposure to sensory and cardiovascular stimuli,” Naunyn Schmiedebergs Arch. Pharmacol., 359, No. 3, 187–193 (1999).

    Article  CAS  PubMed  Google Scholar 

  16. P. D. Londborg, W. T. Smith, V. Glaudin, and J. R. Painter, “Shortterm cotherapy with clonazepam and fl uoxetine: anxiety sleep disturbance and core symptoms of depression,” Affect. Disord., 61, No. 1–2, 73–79 (2000).

    Article  CAS  Google Scholar 

  17. S. Manta, M. El Mansari, G. Debonnel, and P. Blier, “Electrophy siological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems,” Int. Neuropsychopharmacol., 16, No. 2, 459–470 (2013).

    Article  CAS  Google Scholar 

  18. J. Mateo, J. Pineda, and J. J. Meana, “Somatodendritic alpha2-adrenoceptors in the locus coeruleus are involved in the in vivo modulation of cortical noradrenaline release by the antidepressant desipramine,” J. Neurochem., 71, No. 2, 790–798 (1998).

    Article  CAS  PubMed  Google Scholar 

  19. E. J. Nestler, A. McMahon, E. L. Sabban, et al., “Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus,” Proc. Natl. Acad. Sci. USA, 87, No. 19, 7522–7526 (1990).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. T. Pietrasiewicz and I. Zebrowska-Lupina, “Studies on the interaction of antidepressant drugs with adrenocorticotropic hormone or prednisone in rats,” Pol. Pharmacol., 48, No. 2, 145–152 (1996).

    CAS  Google Scholar 

  21. R. D. Porsolt, G. Anton, N. Blavet, and M. Jalfre, “Behavioural despair in rats: a new model sensitive to antidepressant treatments,” Eur. Pharmacol., 47, No. 4, 379–391 (1978).

    Article  CAS  Google Scholar 

  22. N. L. Schramm, M. P. McDonald, and L. E. Limbird, “The alpha [2a]-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety,” J. Neurosci., 21, No. 13, 4875–4882 (2001).

    CAS  PubMed  Google Scholar 

  23. N. Singewald and A. Philippu, “Release of neurotransmitters in the locus coeruleus,” Prog. Neurobiol., 56, No. 2, 237–267 (1998).

    Article  CAS  PubMed  Google Scholar 

  24. N. Singewald, S. T. Kaehler, and A. Philippu, “Noradrenaline release in the locus coeruleus of conscious rats is triggered by drugs stress and blood pressure changes,” Neuroreport, 10, No. 7, 1583–1587 (1999).

    Article  CAS  PubMed  Google Scholar 

  25. S. T. Szabo and P. Blier, “Functional and pharmacological characterization of the modulatory role of serotonin on the fi ring activity of locus coeruleus norepinephrine neurons,” Brain. Res., 922, No. 1, 9–20 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. M. Weinstock, T. Poltyrev, C. Bejar, and M. B. Youdim, “The Effect of TV3326 a novel monoamine-oxidase cholinesterase inhibitor in rat models of anxiety and depression,” Psychopharmacol. (Berlin), 160, No. 3, 318–324 (2002).

    Article  CAS  Google Scholar 

  27. A. Ziomber, P. Thor, A. Krygowska-Wajs, et al., “Chronic impairment of the vagus nerve function leads to inhibition of dopamine but not serotonin neurons in rat brain structures,” Pharmacol. Rep., 64, No. 6, 1359–1367 (2012).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Experimental Medicine, North Western Branch, Russian Academy of Medical Sciences, St. Petersburg, Russia

    S. E. Serdyuk & V. E. Gmiro

Authors
  1. S. E. Serdyuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. E. Gmiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. E. Gmiro.

Additional information

Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 100, No. 1, pp. 18–26, January, 2014.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Serdyuk, S.E., Gmiro, V.E. Mesaton (phenylephrine) Potentiates the Antidepressant and Eliminates the Sedative Action of Amitriptyline in Rats. Neurosci Behav Physi 45, 760–764 (2015). https://doi.org/10.1007/s11055-015-0140-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-015-0140-6

Keywords

Search

Navigation