Advertisement

Neurobehavioral, Neuroendocrine and Neurochemical Effects of Zinc Supplementation in Rats

  • M. Baraldi
  • P. Zanoli
  • A. Benelli
  • M. Sandrini
  • A. Giberti
  • E. Caselgrandi
  • G. Tosi
  • C. Preti
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 203)

Abstract

Extensive morphological and biochemical investigations have been devoted to the neurological effects induced by zinc deficiency since this trace metal has been recognized as essential during neurogenesis for a normal development of the central nervous system (for a review see Dreosti, 1984; Sandstead, 1984). Less attention, however, has been addressed to the neurological consequences of an increased supplementation of zinc.In this context it must be mentioned that the peripheral acute administration of zinc intravenously or intraperitoneally in doses up to 100 mg/kg has not been associated with the production of convulsive seizures or other behavioral abnormalities (Ebadi et al., 1984). From these results, it has been concluded that after parenteral acute administration, zinc does not induce any effect since: a) by binding to circulating proteins such as albumin, gamma-globulins and probably other proteins (Prasad, 1979; Disilvestro and Cousins, 1983; Ebadi et al., 1984) it is unavailable to the CNS; b) it exists mostly in bound form in the brain (Ebadi et al., 1984). In an attempt to gain more information on the behavioral effects induced by peripheral supplementation of zinc, we obtained the same results with regard to the lack of convulsions. In our experience, however, acute intraperitoneal injections of zinc sulphate or zinc acetate induced, in a dose-related fashion starting from 50 mg/kg, a sedative effect which caused a 50% mortality rate within six hours at 200 mg/kg. Based on physiological considerations and on our present observations, it seems more likely to suggest that zinc enters the brain but does not reach concentrations sufficient to induce epileptic seizures which can be elicited by its intracerebroventricular administration (Itoh and Ebadi, 1982; Ebadi et al., 1984). The levels of zinc tested in six brain areas of these rats did not show significant variation in comparison with controls, whereas zinc plasma levels were found to be increased. Time-course determinations of zinc in blood and brain areas are needed in order to explain these data. On the other hand, there are several question marks concerning the machinery which regulates zinc homeostasis in the brain. Thus, it is difficult to explain cerebral zinc uptake and turnover (Kasarskis, 1984) and the unaltered zinc levels in the brain of zinc deficient rats (Wallwork et al., 1983; Kasarskis, 1984) as well as the mechanisms which regulate the bound/free zinc ratio.

Keywords

Adenosine Receptor Epileptic Seizure Anterior Pituitary Opiate Receptor Penile Erection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ahlenius, S., and Larson, K., 1985,. Apomorphine and haloperidol-induced effects on male rat sexual behavior: no evidence for actions due to stimulation of central dopamine autoreceptors, Neurosci. Lett. Suppl., 18: 117.Google Scholar
  2. Baraldi, M., and Bertolini, A., 1974, Penile erections induced by amantadine in male rats, Life Sci., 14: 1231.PubMedCrossRefGoogle Scholar
  3. Baraldi, M., and Benassi-Benelli, A., 1975a, Iduzione di erezioni ripetute nel ratto adulto mediante apomorfina, Riv. Farmacol. Ter., 6: 147.Google Scholar
  4. Baraldi, M., and Benassi-Benelli, A., 1975b, Dissociation of the capacity of apomorphine to evoke penile erection and stereotypy following intra-gastric administration to adult rats, Riv. Farmacol. Ter., 6: 361.Google Scholar
  5. Baraldi, M., and Benassi-Benelli, A., 1977, Sexual excitement induced in the adult male rat by low doses of d-amphetamine or apomorphine:suppression by severe stereotyped behavior, Riv. Farmacol. Ter., 8: 49.Google Scholar
  6. Baraldi, M., Benassi-Benelli, A., Bernabei, M.T., Cameroni, A., Ferrari, F., and Ferrari, P., 1979, Apocodeine induced stereotypies and penile erections in rats, Neuropharmacology, 18: 57.PubMedCrossRefGoogle Scholar
  7. Baraldi, M., Caselgrandi, E., Borella, P., and Zeneroli, M.L., 1983a, Decrease of brain zinc in experimental hepatic encephalophathy, Brain Res. 258: 170.CrossRefGoogle Scholar
  8. Baraldi, M., Poggioli, R., Santi, M., Vergoni, A.V., and Bertolini, A., 1983b, Antidepressant and opiates interactions: pharmacological and biochemical evidence, Pharmaçol, Res. Comm., 15: 843.Google Scholar
  9. Baraldi, M., Caselgrandi, E., and Santi, M., 1984a, Production of withdrawal aymptoms in morphine-dependent rats by zinc: behavioral and biochemical studies, Neurosci. Lett., 18: 5401.Google Scholar
  10. Baraldi, M., Caselgrandi, E., and Santi, M., 1984b, Effect of zinc on specific binding of GABA to rat brain membranes, in: The Neurobiology of Zinc (Part A), C.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, Inc., New York, p. 59.Google Scholar
  11. Baraldi, M., Zeneroli, M.L., Ventura, E., Penne, A., Pinelli,G., Ricci, P., and Santi, M., 1984c, Supersensitivity of benzodiazepine receptors in hepatic encephalopathy due to fulminant hepatic failure in the rat: reversal by a benzodiazepine antagonist, Clin. Sci., 62: 167.Google Scholar
  12. Baraldi, M., 1985, Chronic increase of GABA in vivo as a tool to evidentiate the partial agonistic property of R015-1788 by using an in vitro binding assay, Neurosci. Lett, Sunpl., 18: 31.Google Scholar
  13. Benassi-Benelli, A., Ferrari, F., and Pellegrini-Quarantotti, B., 1978, Penile erection induced by N-n-propyl-norapomorphine in rats, Arch. Int. Pharmacodvn, Ther., 241: 128.Google Scholar
  14. Bertolini, A., and Gessa, G.L., 1981, Behavioral effects of ACTH and MSH peptides, J, Endoerinol, Invest., 4: 421.Google Scholar
  15. Bettger, W.J., and O’Dell, B.L., 1981, A critical physiological role of zinc in the structure and function of biomembranes, Life Sci., 28: 1425.PubMedCrossRefGoogle Scholar
  16. Braestrup, C., Nielsen, M., and Olsen, C.E., 1980,. Urinary and brain ß-carboline-3-carboxylates as a potent inhibitor of brain benzodiazepine receptors, Proc, Natl, Acad. Sci. USA, 77: 2288.CrossRefGoogle Scholar
  17. Brewer, G.S., Ellis, F.B., and Bjork, L., 1981, Parenteral depot method for zinc administration, Pharmacology, 23: 254.PubMedCrossRefGoogle Scholar
  18. Brewer, J., and Oelshlegal, F.J., 1974, Antisuckling effect of zinc, Biochem. Biophys,Res, Comm,. 58: 854.CrossRefGoogle Scholar
  19. Daniel, E.E., Massingham, R., and Nasmyth, P.A., 1970, The mechanism of contractile effects of ouabain and zinc on the rat uterus, J. Pharmacol. Exp. Therap., 173: 293.Google Scholar
  20. Di Chiara, G., Corsini, G.U., Mereu, G.P., Tissari, A., and Gessa, G.L., 1978, Self-inhibitory dopamine receptors: their role in the biochemical and behavioral effects of low doses of apomorphine, in: Adv, Biochem. Psvehopharmacol., P.J. Roberts, ed., Raven Press, New York, p. 275.Google Scholar
  21. Disilvestro, R.A., and Cousins, R.S., 1983, Physiological ligands for copper and zinc, Ann. Rev, Nutr., 3: 261.CrossRefGoogle Scholar
  22. Dreosti, I.E., 1984, Zinc in the central nervous system: the emerging interactions, in: The Neurobiology of Zinc (Part A), C.J. Frederickson, G.A. Howell and E.J. Kasarskis, eds., Alan R. Liss, Inc., New York, p 1.Google Scholar
  23. Ebadi, M., White, R.S., and Swanson, S., 1984, The presence and function of zinc-binding proteins in developing and mature brain, in: The Neurobiology of Zinc (Part A), C.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, New York, p. 39.Google Scholar
  24. Farah, J.M., Sapum Malcolm, J.R.D., and Mueller, J.P., 1982, Dopaminergic inhibition of pituitary ft-endorphin-like immunoreactivity secretion in the rat, Endoçrinology, 110: 657.PubMedCrossRefGoogle Scholar
  25. Fratta, W., Rossetti, Z.L., Poggioli, R., and Gessa, G.L., 1981,. Reciprocal antagonism between ACTH 1_24 and ft-endorphin in rats, Neurosci, Lett., 24: 71.Google Scholar
  26. Gallager, D.W., and Tallman, J.F., 1983,. Consequences of benzodiazepine receptor occupancy, Neuropharmacology, 22: 1493Google Scholar
  27. Hill.D.R., and Bowery, N.C., 1981, 3H-Baclofen and 3H-GABA binding to bicuculline insensitive GABAB sites in rat brain, Nature, 290: 149.Google Scholar
  28. Hjorth, S., Carlsson, A., Clark, D., Swanson, K., Winkinstrum, H., Sanchez, P., Lindberg, P., Hacksell, U., Arvidsson, L.E., Johansson, A., and Nilsson, J.L.G., 1983, Central dopamine receptor agonist and antagonist actions of the enantiomers of 3PPP, Psvchopharmaçologv, 81: 89.CrossRefGoogle Scholar
  29. Itoh, M., and Ebadi, M., 1982, The selective inhibition of hippocampal glutamic acid decarboxylase in zinc-induced epileptic seizures, Neurochem, Res., 7: 1287.CrossRefGoogle Scholar
  30. Izumi, K., Donaldson, J., and Barbeau, A., 1973, Yawning and stretching in rats induced by intraventricularly administered zinc, Life Sci., 12: 203.CrossRefGoogle Scholar
  31. Kasarskis, E.J., 1984, Regulation of zinc homeostasis in rat brain, in: The Neurobiology of Zinc (Part A), C.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, New York, p. 27.Google Scholar
  32. La Bella, F., Dular, R., Stanley, V., and Queen, G., 1973, Pituitary hormone releasing of inhibiting activity of metal ions present in hypothalamic extracts, Biochem. Biophvs. Res. Comm., 52: 786.CrossRefGoogle Scholar
  33. Mackerer, C.R., and Kgchman, R.L., 1978, Effects of cations and anions on the binding of H-diazepam to rat brain, Proc. Soc. Exper. Biol. Med., 158: 393.Google Scholar
  34. Marangos, P.J., Patel, J., Martino, A.M., Dilli, M., and Boulenger, J.P., 1983, Differential binding properties of adenosine receptor agonists and antagonists in brain, J. Neurochem., 41: 367.PubMedCrossRefGoogle Scholar
  35. Meyerson, B., and Terenius, L., 1977, ß-endorphin and male sexual behavior, Eur.J. Pharmacol., 42: 191.PubMedCrossRefGoogle Scholar
  36. Mizumo, S., Ogawa, N., and Mori, A., 1983, Differential effects of some transition metal cations on the binding of ß-carboline-3-carboxylate and diazepam, Neurochem. Res., 8: 873.CrossRefGoogle Scholar
  37. Mogilnicka, E., and Klimek, V., 1977, Drugs affecting dopamine neurons and yawning behaviour, Pharmacol. Biochem, Behay., 7: 305.CrossRefGoogle Scholar
  38. Prasad, A.S., 1979, Clinical, biochemical and pharmacological role of zinc, Ann. Rev. Pharmacol. Toxicol., 20: 393.Google Scholar
  39. Preti, C., and Tosi, G., 1978a, Synthesis and spectroscopic studies on group IIB metal 1-4-benzodiazepine-complexes, Trans. Met. Chem., 3: 246.CrossRefGoogle Scholar
  40. Preti, C., and Tosi, G., 1978b, The complexing behaviour of diazepam towards some bivalent first row transition metals, J. Inorg. Nucl. Chem., 41: 263.CrossRefGoogle Scholar
  41. Petraglia, F., Baraldi, M., Giarre, G., Facchinetti, F., Santi, M., Volpe, A., and Genazzani, A.R., 1985, Opioid peptides of the pituitary and hypothalmus: changes in pregnant and lactating rats, J. Endocrin., 105: 239.CrossRefGoogle Scholar
  42. Sandstead, H.H., 1984, Neurobiology of zinc, in: The Neurobiology of Zinc (Part B), C.J. Frederickson, G.A. Howell, and E.J. Kasarskis, eds., Alan R. Liss, New York, p. 1.Google Scholar
  43. Santi, M., Pinelli, G., Ricci, P., Penne, A., Zeneroli, M.L., and Santi, M., 1985, Evidence that 2-phenylpyrazolo14,3-01-quinolin-3(5H)-one antagonises pharmacological, electrophysiological and biochemical effects of diazepam in rats, Neuropharmaçology, 24: 99.PubMedCrossRefGoogle Scholar
  44. Serra, G., Collu, M., Loddu, S., Celasco, G., and Gessa, G.L., 1983a, Hypophysectomy prevents yawning and penile erection but not hypomotility induced by apomorphine, Pharmacol. Biochem. Behay., 19: 917.CrossRefGoogle Scholar
  45. Serra, G., Fratta, W., Collu, M., Napoli-Farris, L., and Gessa, G.L., 1983b, Cycloheximide prevents apomorphine-induced yawning, penile erection and grooming in rats, Eur. J. Pharmacol., 86: 279.CrossRefGoogle Scholar
  46. Serra, G., Collu, M., Serra, A., and Gessa, G.L., 1984, Estrogens antagonize apomorphine-induced yawning in rats, Europ. J. Pharmacol., 104: 383.CrossRefGoogle Scholar
  47. Simon, E., and Groth, J., 1975, Kinetics of opiate receptor inactivation by sulfhydryl reagents: evidence for conformational change in presence of sodium ions, Proc. Natl. Acad. Sci. USA, 72: 2404.PubMedCrossRefGoogle Scholar
  48. Stengaard-Pedersen, R., 1982, Inhibition of enkephalin binding to opiate receptors by zinc ions: possible physiological importance in the brain, Acta Pharmacol, Toxicol., 50: 213.Google Scholar
  49. Tallman, S.F., Thomas, J.W., and Gallager, D., 1978, GABAergic modulation of benzodiazepine binding site sensitivity, Nature, 272: 383.CrossRefGoogle Scholar
  50. Thody, A.J., Penny, R.J., Taylor, D.C., and Taylor, C., 1975, Development of a radioimmunoassay for a-melanocyte-stimulating hormone, J. Endocrin., 67: 385.CrossRefGoogle Scholar
  51. Tilders, F.J., and Smelik, P.G., 1978, Effects of hypothalamic lesions and drugs interfering with dopaminergic transmission on pituitary MSH content of rats, Neuroendocrinoloav, 25: 275.CrossRefGoogle Scholar
  52. Tseng, L.F., Loh, H., and Li, C.H., 1976, p-Endorphin as a potent analgesic by intravenous injection, Nature, 263: 239.Google Scholar
  53. Wallwork, J.C., Milue, D.B., Sims, R.L., and Sandstead, H.H., 1983, Severe zinc deficiency: effects on the distribution of nine elements (potassium, phosphorous, sodium, magnesium, calcium, iron, zinc, copper and manganese) in regions of rat brain, J. Nutr., 112: 1895.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • M. Baraldi
    • 1
  • P. Zanoli
    • 1
  • A. Benelli
    • 1
  • M. Sandrini
    • 1
  • A. Giberti
    • 1
  • E. Caselgrandi
    • 2
  • G. Tosi
    • 3
  • C. Preti
    • 3
  1. 1.Institute of PharmacologyModena UniversityModenaItaly
  2. 2.Chair of HygieneModena UniversityModenaItaly
  3. 3.Department of ChemistryModena UniversityModenaItaly

Personalised recommendations