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Neuroscience and Behavioral Physiology

, Volume 39, Issue 7, pp 645–653 | Cite as

Features of Central Neurotransmission in Animals in Conditions of Dietary Magnesium Deficiency and After Its Correction

  • A. A. SpasovEmail author
  • I. N. Iezhitsa
  • M. S. Kravchenko
  • M. V. Kharitonova
Article

Magnesium is important in the regulation of neurotransmitter metabolism and the modulation of receptor function in the CNS, including neurotransmitters and receptors involved in the pathogenesis of many mental disorders. The aim of the present work was to perform a pharmacological evaluation of the central mechanisms of action of magnesium salts in the clofelin, phenamine, arecoline, nicotine, apomorphine, and 5-hydroxytryptophan tests in conditions of dietary magnesium deficiency. After reaching the magnesium deficiency state, animals were given oral (via tube) magnesium L-asparaginate and magnesium chloride lone and in combination with vitamin B6, as well as the reference agent Magne B6. Our assessments of phenamine stereotypy in magnesium-deficient animals showed reductions in the latent period by an average of 14.89% and a significant increase in the duration of phenamine stereotypy by an average of 19.44% (from 268.23 ± 8.17 to 320.36 ± 19.90 min) as compared with intact rats. Studies of hyperkinesia induced by 5-hydroxytryptophan showed a two-fold reduction in its extent in the magnesium-deficient group (p ≤ 0.05). Administration of arecoline to magnesium-deficient animals resulted in a statistically significant increase in the latent period from a mean of 92.75 ± 19.35 to 245.17 ± 121.86 sec, with a reduction in the duration of tremor from an average of 1175.58 ± 127.87 to 703.83 ± 89.33 sec (p ≤ 0.05) as compared with intact rats. In terms of its influence on the hypothermic effects of clofelin and apomorphine and the convulsive effect of nicotine, there were no significant differences between the intact group and the magnesium-deficiency animals. Administration of magnesium salts compensated for the magnesium deficiency in plasma and erythrocytes, which was accompanied by recovery of measures in the phenamine, arecoline, and 5-HT tests to levels typical of intact controls. There was a tendency for magnesium L-asparaginate and magnesium chloride combined with pyridoxine to have greater activity, and the efficacies of these treatments was no less than that of reference agent Magne B6. Thus, dietary magnesium deficiency led to impairment of neurotransmission in central serotoninergic, M-cholinergic, and noradrenergic structures and administration of magnesium salts reversed these changes.

Key words

magnesium pyridoxine magnesium deficiency clonidine arecoline nicotine apomorphine 5-hydroxytryptophan rats 

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References

  1. 1.
    N. I. Andreeva, Methodological Recommendations for the Study of the Antidepressant Activity of Pharmacological Substances. Handbook for the Experimental (Preclinical) Study of New Pharmacological Substances [in Russian], Moscow (2000).Google Scholar
  2. 2.
    O. A. Gromova, T. V. Avdeenko, and E. M. Burtsev, “Magnesium deficiency in children with minimal brain dysfunction and its correction with Magne B6,” Klin. Farmakol. Terapiya, 7, No. 3, 52–57 (1998).Google Scholar
  3. 3.
    V. V. Men’shikov, Laboratory Methods for Clinical Studies [in Russian], Meditsina, Moscow (1987).Google Scholar
  4. 4.
    A. A. Spasov, I. N. Iezhitsa, M. V. Kharitonova, and M. S. Kravchenko, “Effects of magnesium salts on the formation of depression-like behavior and anxiety in animals in conditions of dietary magnesium deficiency,” Zh. Vyssh. Nerv. Deyat. imeni I. P. Pavlova (in press).Google Scholar
  5. 5.
    N. Amyard, A. Leyris, C. Monier, H. Frances, R. G. Boulu, and J. G. Henrotte, “Brain catecholamines, serotonin and their metabolites in mice selected for low (MGL) and high (MGH) blood magnesium levels,” Magnes. Res., 8, No. 1, 5–9 (1995).PubMedGoogle Scholar
  6. 6.
    P. Bac, N. Pages, C. Herrenknecht, C. Dewulf, P. Binet, and J. Burlach, “Effect of various serotoninergically induced manipulations on audiogenic seizures in magnesium-deficient mice,” Magnes. Res., 7, No. 2, 107–115 (1994).PubMedGoogle Scholar
  7. 7.
    R. M. Bergman, A. Cappiello, A. Anand, D. A. Oren, G. R. Heininger, D. S. Charney, and J. H. Krystal, “Antidepressant effects of ketamine in depressed patients,” Biol. Psychiatry, 47, 351–354 (2000).CrossRefGoogle Scholar
  8. 8.
    A. Bloc, E. Bugnard, and Y. Dunant, “Acetylcholine synthesis and quantal release reconstituted by transfection of mediatophore and choline acetyl transferase cDNAs,” Eur. J. Neurosci., 11, 1523–1534 (1999).PubMedCrossRefGoogle Scholar
  9. 9.
    G. Choinard, L. Beauclair, R. Geiser, and P. Etienne, “A pilot study of magnesium aspartate hydrochloride (Magnesiocard) as a mood stabilizer for rapid cycling bipolar affective disorder patients,” Prog. Neuropsychopharmacol. Biol. Psychiatr, 14, 171–180 (1990).CrossRefGoogle Scholar
  10. 10.
    J. G. Chutkow and G. M. Tyce, “Brain norepinephrine, dopamine, and 5-hydroxytryptamine in magnesium-deprivation encephalopathy in rats,” J. Neural Transm., 44, No. 4, 297–302 (1979).PubMedCrossRefGoogle Scholar
  11. 11.
    I. M. Cox, M. J. Campbell, and D. Dowson, “Red blood cell magnesium and chronic fatigue syndrome,” Lancet, 337, 757–760 (1991).PubMedCrossRefGoogle Scholar
  12. 12.
    S. Decollogne, A. Tomas, C. Lecerf, E. Adamowicz, and M. Seman, “NMDA receptor complex blockade by oral administration of magnesium: comparison with MK-801,” Pharmacol. Biochem. Behav., 58, No. 1, 261–268 (1997).PubMedCrossRefGoogle Scholar
  13. 13.
    J. Durlach, “Données actuelles sur les mécanismes de synergie entre vitamine B6 et magnesium,” J. Méd. Besançon, 5, 349–359 (1968).Google Scholar
  14. 14.
    J. Durlach, Magnesium in Clinical Practice, John Libbey, London (1988).Google Scholar
  15. 15.
    J. Durlach, V. Durlach, P. Bac, and M. Bara, “Magnesium and therapeutics,” Magnes. Res., 7, No. 3–4, 313–328 (1994).PubMedGoogle Scholar
  16. 16.
    H. El-Beheiry and E. Puil, “Effects of hypomagnesia on transmitter actions in neocortical slices,” Brit. J. Pharmacol., 101, No. 4, 1006–1010 (1990).Google Scholar
  17. 17.
    M. Firoz and M. Graber, “Bioavailability of US commercial magnesium preparations,” Magnes. Res., 14, No. 4, 257–262 (2001).PubMedGoogle Scholar
  18. 18.
    J. E. Holl, A. V. Resurreccion, L. E. Park, and W. O. Caster, “Barbiturate and amphetamine activity in rats fed a magnesium-deficient diet,” Res. Commun. Pathol. Pharmacol., 22, No. 3, 501–512 (1978).Google Scholar
  19. 19.
    I. N. Iezhitsa, A. A. Spasov, M. S. Kravchenko, M. V. Kharitonova, A. A. Ozerov, and I. Yu. Pavlova, “Comparative study of magnesium salts’ bioavailability in rats fed with magnesium-deficient diet. Abstracts of the 11th International Magnesium Symposium & Joint Meeting of the Japanese Society for Magnesium Research,” J. Jap. Soc. Magnes. Res., 25, No. 2, 99–153 (2006).Google Scholar
  20. 20.
    R. A. Janssen and C. Y. Niemegeers, “Is it possible to predict the clinical effects of neuroleptic drugs from animal data? Part IV,” Arzneimittel. Forsch., 17, No. 7, 841–854 (1967).Google Scholar
  21. 21.
    J. D. Kanofsky and R. Sandyk, “Magnesium deficiency in chronic schizophrenia,” Int. J. Neurosci., 61, No. 1–2, 87–90 (1991).PubMedCrossRefGoogle Scholar
  22. 22.
    G. K. Korov, N. J. Birch, P. Steadman, and R. G. Ramsey, “Plasma magnesium levels in a population of psychiatric patients: correlations with symptoms,” Neuropsychobiology, 30, No. 2–3, 73–78 (1994).CrossRefGoogle Scholar
  23. 23.
    J. Levine, D. Stein, A. Rapoport, and L. Kurtzman, “High serum and cerebrospinal fluid Ca/Mg ratio in recently hospitalized acutely depressed patients,” Neuropsychobiology, 39, 63–70 (1999).PubMedCrossRefGoogle Scholar
  24. 24.
    M. Mayer, G. L. Westbrook, and P. B. Guthrie, “Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurons,” Nature, 309, 261–263 (1984).PubMedCrossRefGoogle Scholar
  25. 25.
    M. F. McCarty, “High-dose pyridoxine as an ‘anti-stress’ strategy,” Med. Hypotheses, 54, No. 5, 803–807 (2000).PubMedCrossRefGoogle Scholar
  26. 26.
    R. M. Morris, “Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms,” Magnes. Res., 5, 303–313 (1992).PubMedGoogle Scholar
  27. 27.
    M. Mousain-Bosc,M. Roche, A. Polge, D. Pradal-Prat, J. Rapin, and J. P. Bali, “Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6 I. Attention deficit hyperactivity disorders,” Magnes. Res., 19, No. 1, 46–52 (2006).PubMedGoogle Scholar
  28. 28.
    H. Murck, “Atypical depression spectrum disorder-neurobiology and treatment,” Acta Neuropsychiatrica, 15, 227–241 (2003).CrossRefGoogle Scholar
  29. 29.
    H. Murck, “Magnesium and affective disorders,” Nutr. Neurosci., 5, 375–389 (2002).PubMedCrossRefGoogle Scholar
  30. 30.
    C. S. Paulose, K. Dakshinamurti, S. Packer, and N. L. Stephens, “Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat,” Hypertension, 11, No. 4, 387–391 (1988).PubMedGoogle Scholar
  31. 31.
    E. Planells, A. Lerma, N. Sanchez-Morito, P. Aranda, and J. Lopis, “Effect of magnesium deficiency on vitamin B2 and B6 status in the rat,” J. Amer. Coll. Nutr., 16, No. 4, 352–356 (1997).Google Scholar
  32. 32.
    E. Poleszak and G. Nowak, “Magnesium in pathophysiology and therapy of affective disorders,” J. Element (Biuletyn Magnezologiczny), 11, No. 3, 389–397 (2006).Google Scholar
  33. 33.
    H. H. Rasmussen, P. B. Mortensen, and I. W. Jensen, “Depression and magnesium deficiency,” Int. J. Psychiatry Med., 19, No. 1, 57–63 (1989).PubMedGoogle Scholar
  34. 34.
    S. K. Sharma and K. Dakshinamurti, “Effects of serotonergic agents on plasma prolactin levels in pyridoxine-deficient adult male rats,” Neurochem. Res., 19, No. 6, 687–692 (1994).PubMedCrossRefGoogle Scholar
  35. 35.
    N. Singewalk, C. Sinner, A. Hetzenauer, S. B. Sartori, and H. Murck, “Magnesium-deficient diet alters depression- and anxiety-related behavior in mice-influence of desipramine and Hypericum perforatum extract,” Neuropharmacology, 47, 1189–1197 (2004).Google Scholar
  36. 36.
    P. Skolnick, “Modulation of glutamate receptors: strategies for the development of novel antidepressants,” Amino Acids, 23, 153–159 (2002).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2009

Authors and Affiliations

  • A. A. Spasov
    • 1
    Email author
  • I. N. Iezhitsa
    • 1
  • M. S. Kravchenko
    • 1
  • M. V. Kharitonova
    • 1
  1. 1.Research Institute of Pharmacology and Department of PharmacologyVolgograd State Medical UniversityVolgogradRussia

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