Skip to main content
SpringerLink
Log in

Zinc Chloride and Lead Acetate-Induced Passive Avoidance Memory Retention Deficits Reversed by Nicotine and Bucladesine in Mice

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

It is very important to investigate the neurotoxic effects of metals on learning and memory processes. In this study, we tried to investigate the effects and time course properties of oral administration of zinc chloride (25, 50, and 75 mg/kg, for 2 weeks), lead acetate (250, 750, 1,500, and 2,500 ppm for 4, 6 and 8 weeks), and their possible mechanisms on a model of memory function. For this matter, we examined the intra-peritoneal injections of nicotine (0.25, 0.5, 1, and 1.5 mg/kg) and bucladesine (50, 100, 300, and 600 nM/mouse) for 4 days alone and in combination with mentioned metals in the step-through passive avoidance task. Control animals received saline, drinking water, saline, and DMSO (dimethyl sulfoxide)/deionized water (1:9), respectively. At the end of each part of studies, animals were trained for 1 day in step-through task. The avoidance memory retention alterations were evaluated 24 and 48 h later in singular and combinational studies. Zinc chloride (75 mg/kg) oral gavage for 2 weeks decreased latency times compared to control animals. Also, lead acetate (750 ppm oral administrations for 8 weeks) caused significant lead blood levels and induced avoidance memory retention impairments. Four-days intra-peritoneal injection of nicotine (1 mg/kg) increased latency time compared to control animals. Finally, findings of this research showed that treatment with intra-peritoneal injections of nicotine (1 mg/kg) and/or bucladesine (600 nM/mouse) reversed zinc chloride- and lead acetate-induced avoidance memory retention impairments. Taken together, these results showed the probable role of cholinergic system and protein kinase A pathways in zinc chloride- and lead acetate-induced avoidance memory alterations.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. de Oliveira FS, Viana MR, Antoniolli AR, Marchioro M (2001) Differential effects of lead and zinc on inhibitory avoidance learning in mice. Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas e Biologicas / Sociedade Brasileira de Biofisica [et al.] 34 (1):117–120

  2. Sobotka TJ, Cook MP (1974) Postnatal lead acetate exposure in rats: possible relationship to minimal brain dysfunction. Am J Ment Defic 79(1):5–9

    PubMed  CAS  Google Scholar 

  3. Silbergeld EK, Adler HS (1978) Subcellular mechanisms of lead neurotoxicity. Brain Res 148(2):451–467

    Article  PubMed  CAS  Google Scholar 

  4. Tahmasebi Boroujeni S, Naghdi N, Shahbazi M, Farrokhi A, Bagherzadeh F, Kazemnejad A, Javadian M (2009) The effect of severe zinc deficiency and zinc supplement on spatial learning and memory. Biol Trace Elem Res 130(1):48–61. doi:10.1007/s12011-008-8312-7

    Article  PubMed  CAS  Google Scholar 

  5. Sandstead HH (1985) W.O. Atwater memorial lecture. Zinc: essentiality for brain development and function. Nutr Rev 43(5):129–137

    Article  PubMed  CAS  Google Scholar 

  6. Krigman MR, Druse MJ, Traylor TD, Wilson MH, Newell LR, Hogan EL (1974) Lead encephalopathy in the developing rat: effect upon myelination. J Neuropathol Exp Neurol 33(1):58–73

    Article  PubMed  CAS  Google Scholar 

  7. Alfano DP, Petit TL (1982) Neonatal lead exposure alters the dendritic development of hippocampal dentate granule cells. Exp Neurol 75(2):275–288

    Article  PubMed  CAS  Google Scholar 

  8. Alfano DP, Petit TL (1985) Postnatal lead exposure and the cholinergic system. Physiol Behav 34(3):449–455

    Article  PubMed  CAS  Google Scholar 

  9. Bornschein R, Pearson D, Reiter L (1980) Behavioral effects of moderate lead exposure in children and animal models: part 2, animal studies. Crit Rev Toxicol 8(2):101–152. doi:10.3109/10408448009037492

    Article  PubMed  CAS  Google Scholar 

  10. Bitanihirwe BK, Cunningham MG (2009) Zinc: the brain’s darkhorse. Synapse 63(11):1029–1049. doi:10.1002/syn.20683

    Article  PubMed  CAS  Google Scholar 

  11. Hamadani JD, Fuchs GJ, Osendarp SJ, Huda SN, Grantham-McGregor SM (2002) Zinc supplementation during pregnancy and effects on mental development and behaviour of infants: a follow-up study. Lancet 360(9329):290–294. doi:10.1016/S0140-6736(02)09551-X

    Article  PubMed  CAS  Google Scholar 

  12. Everitt BJ, Robbins TW (1997) Central cholinergic systems and cognition. Annu Rev Psychol 48:649–684. doi:10.1146/annurev.psych.48.1.649

    Article  PubMed  CAS  Google Scholar 

  13. Sarter M, Bruno JP (1997) Cognitive functions of cortical acetylcholine: toward a unifying hypothesis. Brain Res Brain Res Rev 23(1–2):28–46

    Article  PubMed  CAS  Google Scholar 

  14. Francis PT, Palmer AM, Snape M, Wilcock GK (1999) The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 66(2):137–147

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Sharifzadeh M, Zamanian AR, Gholizadeh S, Tabrizian K, Etminani M, Khalaj S, Zarrindast MR, Roghani A (2007) Post-training intrahippocampal infusion of nicotine-bucladesine combination causes a synergistic enhancement effect on spatial memory retention in rats. Eur J Pharmacol 562(3):212–220. doi:10.1016/j.ejphar.2007.01.065

    Article  PubMed  CAS  Google Scholar 

  16. Kim JS, Levin ED (1996) Nicotinic, muscarinic and dopaminergic actions in the ventral hippocampus and thenucleus accumbens: effects on spatial working memory in rats. Brain Res 725(2):231–240

    Article  PubMed  CAS  Google Scholar 

  17. Decker MW, Majchrzak MJ, Anderson DJ (1992) Effects of nicotine on spatial memory deficits in rats with septal lesions. Brain Res 572(1–2):281–285

    Article  PubMed  CAS  Google Scholar 

  18. Frey U, Huang YY, Kandel ER (1993) Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science 260(5114):1661–1664

    Article  PubMed  CAS  Google Scholar 

  19. Abel T, Nguyen PV, Barad M, Deuel TA, Kandel ER, Bourtchouladze R (1997) Genetic demonstration of a role for PKA inthe late phase of LTP and in hippocampus-based long-term memory. Cell 88(5):615–626

    Article  PubMed  CAS  Google Scholar 

  20. Friedrich A, Thomas U, Muller U (2004) Learning at different satiation levels reveals parallel functions for the cAMP-protein kinase A cascade in formation of long-term memory. The Journal of neuroscience : the official journal of the Society for Neuroscience 24(18):4460–4468. doi:10.1523/JNEUROSCI.0669-04.2004

    Article  CAS  Google Scholar 

  21. Adams JP, Roberson ED, English JD, Selcher JC, Sweatt JD (2000) MAPK regulation of gene expression in the central nervous system. Acta Neurobiol Exp 60(3):377–394

    CAS  Google Scholar 

  22. Thiels E, Kanterewicz BI, Norman ED, Trzaskos JM, Klann E (2002) Long-term depression in the adult hippocampus in vivo involves activation of extracellular signal-regulated kinase and phosphorylation of Elk-1. J Neurosci Off J Soc Neurosci 22(6):2054–2062

    CAS  Google Scholar 

  23. Ader R, Weijnen JA, Moleman P (1972) Retention of a passive avoidance response as a function of the intensity and duration of electric shock. Psychon Sci 26(3):125–128

    Article  Google Scholar 

  24. Shah F, Kazi TG, Afridi HI, Naeemullah AMB, Baig JA (2011) Cloud point extraction for determination of lead in blood samples of children, using different ligands prior to analysis by flame atomic absorption spectrometry: a multivariate study. J Hazard Mater 192(3):1132–1139. doi:10.1016/j.jhazmat.2011.06.017

    Article  PubMed  CAS  Google Scholar 

  25. Cuajungco MP, Goldstein LE, Nunomura A, Smith MA, Lim JT, Atwood CS, Huang X, Farrag YW, Perry G, Bush AI (2000) Evidence that the beta-amyloid plaques of Alzheimer’s disease represent the redox-silencing and entombment of a beta by zinc. J Biol Chem 275(26):19439–19442. doi:10.1074/jbc.C000165200

    Article  PubMed  CAS  Google Scholar 

  26. Chowanadisai W, Kelleher SL, Lonnerdal B (2005) Maternal zinc deficiency reduces NMDA receptor expression in neonatal rat brain, which persists into early adulthood. J Neurochem 94(2):510–519. doi:10.1111/j.1471-4159.2005.03246.x

    Article  PubMed  CAS  Google Scholar 

  27. Brun VH, Ytterbo K, Morris RG, Moser MB, Moser EI (2001) Retrograde amnesia for spatial memory induced by NMDA receptor-mediated long-term potentiation. J Neurosci OffJ Soc Neurosci 21(1):356–362

    CAS  Google Scholar 

  28. Morris RG (1989) Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5. J Neurosci OffJ Soc Neurosci 9(9):3040–3057

    CAS  Google Scholar 

  29. Ebuehi OAT, Akande GA (2008) Effect of zinc deficiency on memory, oxidative stress and blood chemistry in rats. Adv Med Dent Sci 2:74–82

    CAS  Google Scholar 

  30. von Bulow V, Dubben S, Engelhardt G, Hebel S, Plumakers B, Heine H, Rink L, Haase H (2007) Zinc-dependent suppression of TNF-alpha production is mediated by protein kinase A-induced inhibition of Raf-1, I kappa B kinase beta, and NF-kappa B. J Immunol 179(6):4180–4186

    Article  Google Scholar 

  31. Honscheid A, Dubben S, Rink L, Haase H (2012) Zinc differentially regulates mitogen-activated protein kinases in human T cells. J Nutr Biochem 23(1):18–26. doi:10.1016/j.jnutbio.2010.10.007

    Article  PubMed  CAS  Google Scholar 

  32. Hogstedt C, Hane M, Agrell A, Bodin L (1983) Neuropsychological test results and symptoms among workers with well-defined long-term exposure to lead. Br J Ind Med 40(1):99–105

    PubMed  PubMed Central  CAS  Google Scholar 

  33. Williamson AM, Teo RK (1986) Neurobehavioural effects of occupational exposure to lead. Br J Ind Med 43(6):374–380

    PubMed  PubMed Central  CAS  Google Scholar 

  34. Vazquez A, Pena de Ortiz S (2004) Lead (Pb(+2)) impairs long-term memory and blocks learning-induced increases in hippocampal protein kinase C activity. Toxicol Appl Pharmacol 200(1):27–39. doi:10.1016/j.taap.2004.03.011

    Article  PubMed  CAS  Google Scholar 

  35. Jett DA, Kuhlmann AC, Guilarte TR (1997) Intrahippocampal administration of lead (Pb) impairs performance of rats in the Morris water maze. Pharmacol Biochem Behav 57(1–2):263–269

    Article  PubMed  CAS  Google Scholar 

  36. Rodrigues AL, Rubin MA, Souza DO, de Mello CF (1993) Lead exposure and latent learning ability of adult female rats. Behav Neural Biol 60(3):274–279

    Article  PubMed  CAS  Google Scholar 

  37. Toscano CD, Guilarte TR (2005) Lead neurotoxicity: from exposure to molecular effects. Brain Res Brain Res Rev 49(3):529–554. doi:10.1016/j.brainresrev.2005.02.004

    Article  PubMed  CAS  Google Scholar 

  38. Sandhir R, Gill KD (1994) Lead perturbs calmodulin dependent cyclic AMP metabolism in rat central nervous system. Biochem Mol Biol Int 33(4):729–742

    PubMed  CAS  Google Scholar 

  39. Reddy GR, Devi BC, Chetty CS (2007) Developmental lead neurotoxicity: alterations in brain cholinergic system. Neurotoxicology 28(2):402–407. doi:10.1016/j.neuro.2006.03.018

    Article  PubMed  CAS  Google Scholar 

  40. Gietzen DW, Woolley DE (1984) Acetylcholinesterase activity in the brain of rat pups and dams after exposure to lead via the maternal water supply. Neurotoxicology 5(3):235–246

    PubMed  CAS  Google Scholar 

  41. Perry EK, Perry RH, Blessed G, Tomlinson BE (1977) Necropsy evidence of central cholinergic deficits in senile dementia. Lancet 1(8004):189

    Article  PubMed  CAS  Google Scholar 

  42. Azami K, Etminani M, Tabrizian K, Salar F, Belaran M, Hosseini A, Hosseini-Sharifabad A, Sharifzadeh M (2010) The quantitative evaluation of cholinergic markers in spatial memory improvement induced by nicotine-bucladesine combination in rats. Eur J Pharmacol 636(1–3):102–107. doi:10.1016/j.ejphar.2010.03.041

    Article  PubMed  CAS  Google Scholar 

  43. Tabrizian K, Najafi S, Belaran M, Hosseini-Sharifabad A, Azami K, Hosseini A, Soodi M, Kazemi A, Abbas A, Sharifzadeh M (2010) Effects of selective iNOS inhibitor on spatial memory in recovered and non-recovered ketamine induced-anesthesia in Wistar rats. Iran J Pharm Res 9(3):313–320

    PubMed  PubMed Central  CAS  Google Scholar 

  44. Dajas-Bailador FA, Mogg AJ, Wonnacott S (2002) Intracellular Ca2+ signals evoked by stimulation of nicotinic acetylcholine receptors in SH-SY5Y cells: contribution of voltage-operatedCa2+ channels and Ca2+ stores. J Neurochem 81(3):606–614

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

    Kaveh Tabrizian, Abdolmajid Yazdani, Behnam Baheri & Mahmoud Hashemzaei

  2. Medicinal Plants Research Center, Zabol University of Medical Sciences, Zabol, Iran

    Kaveh Tabrizian & Abdolhossein Miri

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran

    Borna Payandemehr, Mehdi Sanati & Mohammad Sharifzadeh

  4. Department of Pharmacognosy, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

    Abdolhossein Miri

  5. Department of Pharmaceutics, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

    Majid Zandkarimi

  6. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Belaran

  7. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Sahar Fanoudi

Authors
  1. Kaveh Tabrizian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdolmajid Yazdani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Behnam Baheri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Borna Payandemehr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehdi Sanati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mahmoud Hashemzaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Abdolhossein Miri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Majid Zandkarimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maryam Belaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sahar Fanoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mohammad Sharifzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Sharifzadeh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tabrizian, K., Yazdani, A., Baheri, B. et al. Zinc Chloride and Lead Acetate-Induced Passive Avoidance Memory Retention Deficits Reversed by Nicotine and Bucladesine in Mice. Biol Trace Elem Res 169, 106–113 (2016). https://doi.org/10.1007/s12011-015-0399-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0399-z

Keywords

Search

Navigation