The Effects of Zinc on the Central Dopaminergic System of Rats Prenatally Exposed to Cadmium
A. Durczok1, R. Szkilnik1, P. Nowak1, Ł. Labus1, J. Dąbrowska1, A. Bortel1, T. Zagził1,
M. Swoboda1, W. Rycerski1, H. Winnicka2, R. M. Kostrzewa3, A. Kwieciński1, R. Brus1
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1Department of Pharmacology, Medical University of Silesia, ul. Jordana 38, 41-808 Zabrze, Poland.
2Central Laboratory of Heavy Metal Toxicology, Zinc Smelting Works, 42-610 Tarnowskie Góry, Poland
3East Tennessee State University, Quillen College of Medicine, Department of Pharmacology, Johnson City, TN 37614, USA
Pol. J. Environ. Stud. 2005;14(5):569–576
On the morning of the first day of pregnancy, Wistar rats were administered a single IP injection of either zinc sulfate (10.0 mg/kg) or saline. For the remainder of pregnancy, half the rats in each group then consumed filtered tap water while the other half consumed filtered tap water with 50 ppm of cadmium (CdCl2). At eight weeks after birth, the behavioral profile of male offspring was assessed in the following way: Apomorphine (non-selective dopamine receptor agonist), (+)-7-hydroxy-2-(di-n-propylamino) tetralin (7-OH-DPAT) (D agonist) and (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393) (D1 agonist) were used to evaluate stereotyped behavior, yawning activity and oral movements - indices for these respective agonists. In addition, two dopamine receptor antagonists, haloperidol (D2 antagonist) and 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzapine (SCH 23390) (D1 antagonist) were used to evaluate cataleptogenic activity. Additional behavioral parameters studied were locomotor activity, irritability and reaction to a painful stimulus. Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) were quantified in the striatum, hippocampus and in the frontal cortex of the brain by means of HPLC/ED technique. In addition, cadmium levels were analyzed in the brain, liver, kidney and bone of newborn rats. Our results indicate that prenatal exposure of pregnant rats to cadmium produced alterations in the reactivity of central dopamine receptors and modulated the level of dopamine and its metabolites in the offsprings' brains. A single injection of zinc, preceding cadmium consumption, attenuated some of the effects of cadmium on the offsprings' dopaminergic system. Zinc also reduced cadmium deposition in the brain, kidney and bone, but enhanced its accumulation in liver. In summary, zinc may exert some neuroprotective effects against cadmium neurotoxicity.