Skip to main content
Log in

Short term cadmium administration dose dependently elicits immediate biochemical, neurochemical and neurobehavioral dysfunction in male rats

  • Research Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Cadmium is a toxic environmental and industrial pollutant. Cadmium toxicity has been reported to produce biochemical and behavioral dysfunction that may cause adverse effects on several organs including the central nervous system. The present study was designed to investigate the neurotoxic effects of Cadmium Chloride (CdCl2) at three different doses by using different behavioral models. Lipid peroxidation (LPO), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities were also monitored following acute intraperitoneal injection of cadmium. Twenty four adult locally bred Albino Wistar rats were divided into control and 3 test groups (n = 6). Control rats were injected intraperitoneally with saline (0.9 % NaCl) and test groups were injected with CdCl2 (1 mg/kg, 2 mg/kg and 3 mg/kg) dissolved in physiological solution. Behavioral activities of rats were monitored after 1 h of cadmium injection. Locomotor activity and depression-like symptoms were measured by Open Field Test (OFT) and Forced Swimming Test (FST) respectively. Anxiety like behavior was monitored using Light–dark Transition (LDT) test and memory functions of rats were assessed by Morris Water Maze test (MWM). In the present study acute cadmium administration dose dependently increased anxiety in rats as compared to control rats. A significant increase in depression-like symptoms was also exhibited by cadmium treated rats. These behavioral dysfunctions may be attributed to the decreased superoxide dismutase (SOD) activity and simultaneously increased brain lipid peroxidation (LPO). Moreover learning and memory assessed by MWM showed dose dependent impairment in memory function in cadmium treated rats as compared to control rats. Acetylcholinesterase (AChE) activity was also decreased in brains of cadmium administered rats. It is suggested in this study that behavioral, biochemical and neurochemical dysfunctions caused by acute cadmium administration occur in a dose dependent manner.

This is a preview of subscription content, log in via an institution to check access.

Access this article

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
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

5-HT:

5-hydroxytryptamine

BBB:

Blood brain barrier

CdCl2 :

Cadmium Chloride

FST:

Forced swimming test

LDT:

Light–dark transition

MWM:

Morris water maze

OFT:

Open field test

AChE:

Acetylcholinesterase

LPO:

Lipid peroxidation

SOD:

Superoxide dismutase

ATC:

Acetylthiocholine

References

  • Andersson H, Petersson-Grawé K, Lindqvist E, Luthman J, Oskarsson A, Olson L (1997) Low-level cadmium exposure of lactating rats causes alterations in brain serotonin levels in the offspring. Neurotoxicol Teratol 19:105–115

    Article  CAS  PubMed  Google Scholar 

  • Beauchamp C, Fridovich I (1971) Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem 44:276–287

  • Bouayed J, Rammal H, Soulimani R (2009) Oxidative stress and anxiety. Oxid Med Cell Longev 2:63–67

    Article  PubMed Central  PubMed  Google Scholar 

  • Bull S (2010) Cadmium: toxicological Overview CHAPD HQ HPA–version 3:1–15

  • Carageorgiou HV, Tzotzes V, Pantos C, Mourouzis C, Zarros A, Tsakiris S (2004) In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, on adult rat brain total antioxidant status, acetylcholinesterase, cysteine. Basic Clin Pharmacol Toxicol 94:112–118

    Article  CAS  PubMed  Google Scholar 

  • Carageorgiou H, Tzotzes V, Sideris A, Zarros A, Tsakiris S (2005) Cadmium effects on brain acetylcholinesterase activity and antioxidant status of adult rats: modulation by zinc, calcium and L-cysteine co-administration. Basic Clin Pharmacol Toxicol 97:320–324

    Article  CAS  PubMed  Google Scholar 

  • Chidambara Murthy KN, Jayaprakasha GK, Singh RP (2002) Studies on antioxidant activity of pomegranate (Punicagranatum) peel extract using in vivo models. J Agric Food Chem 50:4791–4795

  • Chkhartishvili E, Maglakelidze N, Babilodze M, Chijavadze E, Nachkebia N (2011) Changes of open field behavior in animal model of depression. Georgian Med News 11:107–112

    CAS  PubMed  Google Scholar 

  • Cordell D, Rosemarin A, Schröder JJ, Smit AL (2011) Towards global phosphorus security: a systems framework for phosphorus recovery and reuse options. Chemosphere 84:747–758

    Article  CAS  PubMed  Google Scholar 

  • De Castro E, Silva E, Ferreira H, Cunha M, Bulcão C, Sarmento C, De Oliveira I, Fregoneze JB (1996) Effect of central acute administration of cadmium on drinking behavior. Pharmacol Biochem Behav 53:687–693

    Article  Google Scholar 

  • De La Torre FR, Ferrari L, Salibian A (2002) Freshwater pollution biomarker: response of brain acetylcholinesterase activity in two fish species. Comp Biochem Physiol C 131:271–280

    Article  Google Scholar 

  • De’si I, Nagymajte’nyi L, Schulz H (1999) Behavioural and neurotoxicological changes caused by cadmium treatment of rats during development. J Appl Toxicol 18:63–70

    Article  Google Scholar 

  • Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholine esterase activity. Biochem Pharmacol 7:88–95

  • Gagnaire B, Adam-Guillermin C, Bouron A, Lestaevel P (2011) The effects of radionuclides on animal behavior. Rev Environ Contam Toxicol 210:35–58

    CAS  PubMed  Google Scholar 

  • Haider S, Tabassum S, Perveen T, Ali S, Saleem S, Khan AK, Haleem DJ (2011) Age-related decrease in striatal DA produces cognitive deficits in male rats. J Pharm Nutr Sci 1:20–27

    Article  Google Scholar 

  • Haleem DJ, Batool F (1996) Regionally specific effects of diazepam on brain serotonin metabolism in rats: sustained effects following repeated administration. Life Sci 59:239–246

    Article  Google Scholar 

  • Jacob RA, Burri BJ (1996) Oxidative damage and defense. Am J Clin Nutr 63:985–990

    Google Scholar 

  • Järup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182

    Article  PubMed  Google Scholar 

  • Jones MM, Cherian C (1990) Cadmium, a unique metal. Toxicolog-y J 62:1–25

    Article  CAS  Google Scholar 

  • Kaoud HA, Kamel MM, Abdel-Razek AH, Kamel GM, Ahmed KA (2010) Neurobehavioural, neurochemical and neuromorphological effects of cadmium in male rats. J Am Sci 6:189–202

    Google Scholar 

  • Kennett GA, Dickinson SL, Curzon G (1985) Central serotonergic responses and behavioral adaptation to repeated immobilization: the effect of corticosterone synthesis inhibitor metyrapone. Eur J Pharmacol 119:143–152

    Article  CAS  PubMed  Google Scholar 

  • Lafuente A, Fenández-Rey E, Seara R, Pérez-Lorenzo M, Esquifino AI (2001) Alternate cadmium exposure differentially affects amino acid metabolism within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats. Neurochem Int 39:187–192

    Article  CAS  PubMed  Google Scholar 

  • Lafuente A, González-Carracedo A, Romero A, Esquifino AI (2003) Effect of cadmium on 24-h variations in hypothalamic dopamine and serotonin metabolism in adult male rats. Exp Brain Res 149:200–206

    CAS  PubMed  Google Scholar 

  • Leret ML, Millan JA, Antonio MT (2003) Perinatal exposure to lead and cadmium affects anxiety-like behaviour. Toxicology 186:125–130

    Article  CAS  PubMed  Google Scholar 

  • Lionetto MG, Caricato R, Giordano ME, Pascariello MF, Marinosci L, Schettino T (2003) Integrated use of biomarkers (acetylcholineasterase and antioxidant enzymes activities) in Myulus galloprovincialis and Mullus barbatus in an Italian coastal marine area. Mar Pollut Bull 46:324–330

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Rodriguez F, Kim J, Poland RE (2004) Total sleep deprivation decreases immobility in the forced-swim test. Neuropsychopharmacology 29:1105–1111

    Article  CAS  PubMed  Google Scholar 

  • Lukawski K, Nieradko B, Sieklucka-Dziuba M (2005) Effects of cadmium on memory processes in mice exposed to transient cerebral oligemia. Neurotoxicol Teratol 27:575–584

    Article  CAS  PubMed  Google Scholar 

  • Méndez-Armenta M, Ríos C (2007) Cadmium neurotoxicity. Environ Toxicol Pharmacol 23:350–358

    Article  PubMed  Google Scholar 

  • Milic VD, Stankov K, Injac R, Djordjevic A, Srdjenovic B, Govedarica B (2009) Activity of antioxidative enzymes in erythrocytes after a single dose administration of doxorubicin in rats pretreated with fullerenol C(60)(OH)(24). Toxicol Mech Methods 19:24–28

    Article  CAS  PubMed  Google Scholar 

  • Morris RGM (1981) Spatial localization does not depend on the presence of local cues. Learning Motiv 12:239–260

    Article  Google Scholar 

  • Murphy VA (1997) Cadmium: acute and chronic neurological disorders. In: Yasui M, Strong M, Ota K, Verity MA (eds) Mineral and Metal Neurotoxicology. CRC press, Boca Raton, pp 229–240

    Google Scholar 

  • Newsome WH, Davies D, Doucet J (1995) PCB and organochlorine pesticides in Canadian human milk. Chemosphere 30:2143–2153

    Article  CAS  PubMed  Google Scholar 

  • Nishimura Y, Yamaguchi JY, Kanada A, Horimoto K, Kanemaru K, Satoh M, Oyama Y (2006) Increase in intracellular Cd (2+) concentration of rat cerebellar granule neurons incubated with cadmium chloride: cadmium cytotoxicity under external Ca (2+)–free condition. Toxicol In Vitro 20:211–216

    Article  CAS  PubMed  Google Scholar 

  • Pari L, Murugavel P (2007) Diallyl tetrasulfide improves cadmium induced alterations of acetylcholinesterase, ATPases and oxidative stress in brain of rats. Toxicology 234:44–50

    Article  CAS  PubMed  Google Scholar 

  • Rastogi RB, Merali Z, Singhal RL (1977) Cadmium alters behaviour and the biosynthetic capacity for catecholamines and serotonin in neonatal rat brain. J Neurochem 28:789–794

    Article  CAS  PubMed  Google Scholar 

  • Romero A, Caride A, Pereiro N, Lafuente A (2011) Modulatory effects of melatoninon cadmium-induced changes in biogenic amines in rat hypothalamus. Neurotox Res 20:240–249

    Article  CAS  PubMed  Google Scholar 

  • Rose CS, Heywood PG, Costanzo RM (1992) Olfactory impairment after chronic occupational cadmium exposure. J Occup Med 34:600–605

    CAS  PubMed  Google Scholar 

  • Salehi B, Cordero MI, Sandi C (2010) Learning under stress: the inverted-U-shape function revisited. Learn Mem 17:522–530

    Article  PubMed  Google Scholar 

  • Sarkar S, Yadav P, Trivedi R, Bansal AK, Bhatnagar D (1995) Cadmium-induced lipid peroxidation and the status of the antioxidant system in rat tissues. J Trace Elem Med Biol 9:144–149

    Article  CAS  PubMed  Google Scholar 

  • Sarkar S, Yadav P, Bhatnagar DJ (1998) Lipid peroxidative damage on cadmium exposure and alterations in antioxidant system in rat erythrocytes: A study with relation to time. Biometals 11:153–157

    Article  CAS  PubMed  Google Scholar 

  • Senger MR, Rosemberg DB, Rico EP, de Bem Arizi M, Dias RD, Bogo MR, Bonan CD (2006) In vitro effect of zinc and cadmium on acetylcholinesterase and ectonucleotidase activities in zebrafish (Danio rerio) brain. Toxicol In Vitro 20:954–958

  • Shukla A, Shukla GS, Srimal RC (1996) Cadmium-induced alterations in blood–brain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat. Hum Exp Toxicol 15:400–405

    Article  CAS  PubMed  Google Scholar 

  • Tomlinson G, Mutus B, McLennan I (1981) Activation and inactivation of acetylcholinesterase by metal ions. Can J Biochem 59:728–735

    Article  CAS  PubMed  Google Scholar 

  • Wong KL, Klaassen CD (1982) Neurotoxic effects of cadmium in young rats. Toxicol Appl Pharmacol 63:330–337

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are thankful to the University of Karachi, Pakistan for funding this project.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Saida Haider.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Haider, S., Anis, L., Batool, Z. et al. Short term cadmium administration dose dependently elicits immediate biochemical, neurochemical and neurobehavioral dysfunction in male rats. Metab Brain Dis 30, 83–92 (2015). https://doi.org/10.1007/s11011-014-9578-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-014-9578-4

Keywords

Navigation