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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
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.
Baraldi, M., and Bertolini, A., 1974, Penile erections induced by amantadine in male rats, Life Sci., 14: 1231.
Baraldi, M., and Benassi-Benelli, A., 1975a, Iduzione di erezioni ripetute nel ratto adulto mediante apomorfina, Riv. Farmacol. Ter., 6: 147.
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.
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.
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.
Baraldi, M., Caselgrandi, E., Borella, P., and Zeneroli, M.L., 1983a, Decrease of brain zinc in experimental hepatic encephalophathy, Brain Res. 258: 170.
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.
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.
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.
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.
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.
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.
Bertolini, A., and Gessa, G.L., 1981, Behavioral effects of ACTH and MSH peptides, J, Endoerinol, Invest., 4: 421.
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.
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.
Brewer, G.S., Ellis, F.B., and Bjork, L., 1981, Parenteral depot method for zinc administration, Pharmacology, 23: 254.
Brewer, J., and Oelshlegal, F.J., 1974, Antisuckling effect of zinc, Biochem. Biophys,Res, Comm,. 58: 854.
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.
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.
Disilvestro, R.A., and Cousins, R.S., 1983, Physiological ligands for copper and zinc, Ann. Rev, Nutr., 3: 261.
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.
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.
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.
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.
Gallager, D.W., and Tallman, J.F., 1983,. Consequences of benzodiazepine receptor occupancy, Neuropharmacology, 22: 1493
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.
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.
Itoh, M., and Ebadi, M., 1982, The selective inhibition of hippocampal glutamic acid decarboxylase in zinc-induced epileptic seizures, Neurochem, Res., 7: 1287.
Izumi, K., Donaldson, J., and Barbeau, A., 1973, Yawning and stretching in rats induced by intraventricularly administered zinc, Life Sci., 12: 203.
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.
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.
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.
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.
Meyerson, B., and Terenius, L., 1977, ß-endorphin and male sexual behavior, Eur.J. Pharmacol., 42: 191.
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.
Mogilnicka, E., and Klimek, V., 1977, Drugs affecting dopamine neurons and yawning behaviour, Pharmacol. Biochem, Behay., 7: 305.
Prasad, A.S., 1979, Clinical, biochemical and pharmacological role of zinc, Ann. Rev. Pharmacol. Toxicol., 20: 393.
Preti, C., and Tosi, G., 1978a, Synthesis and spectroscopic studies on group IIB metal 1-4-benzodiazepine-complexes, Trans. Met. Chem., 3: 246.
Preti, C., and Tosi, G., 1978b, The complexing behaviour of diazepam towards some bivalent first row transition metals, J. Inorg. Nucl. Chem., 41: 263.
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.
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.
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.
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.
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.
Serra, G., Collu, M., Serra, A., and Gessa, G.L., 1984, Estrogens antagonize apomorphine-induced yawning in rats, Europ. J. Pharmacol., 104: 383.
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.
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.
Tallman, S.F., Thomas, J.W., and Gallager, D., 1978, GABAergic modulation of benzodiazepine binding site sensitivity, Nature, 272: 383.
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.
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.
Tseng, L.F., Loh, H., and Li, C.H., 1976, p-Endorphin as a potent analgesic by intravenous injection, Nature, 263: 239.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1986 Plenum Press, New York
About this chapter
Cite this chapter
Baraldi, M. et al. (1986). Neurobehavioral, Neuroendocrine and Neurochemical Effects of Zinc Supplementation in Rats. In: Schwarcz, R., Ben-Ari, Y. (eds) Excitatory Amino Acids and Epilepsy. Advances in Experimental Medicine and Biology, vol 203. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7971-3_44
Download citation
DOI: https://doi.org/10.1007/978-1-4684-7971-3_44
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-7973-7
Online ISBN: 978-1-4684-7971-3
eBook Packages: Springer Book Archive