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Altered central monoamine response tod-amphetamine in rats chronically exposed to inorganic lead

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Abstract

Investigations of the mechanisms involved in the neurotoxicity resulting from chronic inorganic lead (Pb) exposure have centered on CNS biogenic amine function on the basis of behavioral and neurochemical findings. The following study examined the time course of the response of dopamine (DA) and 5-hydroxytryptamine (5-HT) neurons to d-amphetamine (AMPH) in rats chronically exposed to Pb from birth in order to further examine neurochemical mechanisms implicated by previous work. Offspring were exposed to 0.2% Pb acetate via the lactating dam and then weaned to the same drinking solution. At 120–140 days animals were injected with 1.0 mg/kg s.c. of the drug or with saline and sacrificed after various intervals. DA content in nucleus accumbens and corpus striatum in Pb-exposed animals was significantly higher than corresponding levels in controls at 20 minutes post-drug and remained significantly higher than baseline values at 80 minutes after the drug when DA concentrations in controls had returned to normal. These data suggest enhanced AMPH-induced DA synthesis in exposed rats. 5-Hydroxyindoleacetic acid (5-HIAA) content was significantly increased in three brain regions in exposed rats given AMPH compared to values in saline-injected exposed animals, indicating a compensation in these areas for the decreases in 5-HIAA values produced by Pb exposure alone. The results of this study reinforce the hypothesis that DA and 5-HT neurons are sensitive to relatively low levels of Pb exposure.

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References

  1. Applegate, C. D., andKuczenski, R. 1983. Amphetamine-induced changes in serotonin metabolism: Opposite effects in hippocampus and striatum. Soc. Neurosci. Abstr. 9:878.

    Google Scholar 

  2. Bunney, B. S., Walters, J. R., Roth, R. H., andAghajanian, G. K. 1973. Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single cell activity. J. Pharmacol. Exp. Ther. 185:560–571.

    Google Scholar 

  3. Bunney, B. S., andAghajanian, G. K. 1978. d-Amphetamine-induced depression of central dopamine neurons: Evidence for mediation by both autoreceptors and striatonigral feedback pathway. Naunyn-Schmiede. Arch. Pharmacol. 304:255–261.

    Google Scholar 

  4. Carter, C. J., andPycock, C. J. 1979. The effects of 5,7-dihydroxytryptamine lesions of extrapyramidal and mesolimbic sites on spontaneous motor behavior and amphetamine-induced stereotypy. Naunyn-Schmiede. Arch. Pharmacol. 308:51–54.

    Google Scholar 

  5. Chisolm, J. J., andBrown, D. H. 1975. Micro-scale photofluorometric determination of ‘free erythrocyte porphyrin’ (protoporphyrin IX). Clin. Chem. 21:1669–1682.

    Google Scholar 

  6. Coleman, W. E., andTardiff, R. G. 1979. Contaminant levels in animal feeds used for toxicity studies. Arch. Environ. Contam. Toxicol. 8:693–702.

    Google Scholar 

  7. Costall, B., Hui, S.-C. G., andNaylor, R. J. The importance of serotonergic mechanisms for the induction of hyperactivity by amphetamine and its antagonism by intra-accumbens (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI). Neuropharmacology 18:605–609.

  8. Dubas, T. C., Stevenson, A., Singhal, R. L., andHrdina, P. D. 1978. Regional alterations of brain biogenic amines in young rats following chronic lead exposure. Toxicol. 9:185–190.

    Google Scholar 

  9. Heffner, T. G., Hartman, J. A., andSeiden, L. S. 1980. A rapid method for the regional dissection of the rat brain. Pharmacol. Biochem. Behav. 13:453–456.

    Google Scholar 

  10. Isaacson, R. L. 1980. Limbic system contributions to goal-directed behavior. Pages 409–423,in Thompson, R. F., Hicks, L. H., andShvyrkov, B. V. (eds.), neural mechanisms of goal-directed behavior and learning. Academic Press, New York.

    Google Scholar 

  11. Jason, K. M., andKellogg, C. K. 1981. Neonatal lead exposure: Effects on development of behavior and striatal dopamine neurons. Pharmacol. Biochem. Behav. 15:641–649.

    Google Scholar 

  12. Kelly, P. H., Seviour, P. W., andIversen, S. D. 1975. Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 94:507–522.

    Google Scholar 

  13. Kostas, J., McFarland, D. J., andDrew, W. G. 1978. Lead-induced behavioral disorders in the rat: Effects of amphetamine. Pharmacology 16:226–236.

    Google Scholar 

  14. Kuczenski, R. 1979. Effects of para-chlorophenylalanine on amphetamine and haloperidol-induced changes in striatal dopamine turnover. Brain Res. 164:217–225.

    Google Scholar 

  15. Kuczenski, R. 1980. Amphetamine-haloperidol interactions on striatal and mesolimbic tyrosine hydroxylase activity and dopamine metabolism. J. Pharmacol. Exp. Ther. 215:135–142.

    Google Scholar 

  16. Lasley, S. M., Michaelson, I. A., Greenland, R. D., andMcGinnis, P. M. 1984. Simultaneous measurement of tyrosine and tryptophan and related monoamines for determination of neurotransmitter turnover in discrete rat brain regions by liquid chromatography with electrochemical detection. J. Chromatogr. 305:27–42.

    Google Scholar 

  17. Lasley, S. M., Greenland, R. D., Minnema, D. J., andMichaelson, I. A. 1984. Influence of chronic inorganic lead exposure on regional dopamine and 5-hydroxytryptamine turnover in rat brain. Neurochem. Res. 9:1675–1688.

    Google Scholar 

  18. Lucchi, L., Memo, M., Airaghi, M. L., Spano, P. F., andTrabucchi, M. 1981. Chronic lead treatment induces in rat a specific and differential effect on dopamine receptors in different brain areas. Brain Res. 213:397–404.

    Google Scholar 

  19. Memo, M., Lucchi, L., Spano, P. F., andTrabucchi, M. 1980. Lack of correlation between the neurochemical and behavioral effects induced by d-amphetamine in chronically lead-treated rats. Neuropharmacology 19:795–799.

    Google Scholar 

  20. Memo, M., Lucchi, L., Spano, P. F., andTrabucchi, M. 1981. Dose-dependent and reversible effects of lead on rat dopaminergic system. Life Sci. 28:795–799.

    Google Scholar 

  21. Moore, K. E., andWuerthele, S. M. 1979. Regulation of nigrostriatal and tuberoinfundibular-hypophyseal dopaminergic neurons. Prog. Neurobiol. 13:325–359.

    Google Scholar 

  22. Nielsen, E. B., andScheel-Kruger, J. 1984. Amphetamine cue: Elicitation by intraaccumbens microinjection. Soc. Neurosci. Abstr. 10:1072.

    Google Scholar 

  23. Pijnenberg, A. J. J., Honig, W. M. M., van der Heyden, J. A. M., andvan Rossum, J. M. 1976. Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Eur. J. Pharmacol. 35:45–58.

    Google Scholar 

  24. Rafales, L. S., Bornschein, R. L., Michaelson, I. A., Loch, R. K., andBarker, G. F. 1979. Drug-induced activity in lead-exposed mice. Pharmacol. Biochem. Behav. 10:95–104.

    Google Scholar 

  25. Fafales, L. S., Lasley, S. M., Greenland, R. D., andMandybur, T. 1983. Effects of acrylamide on locomotion and central monoamine function in the rat. Pharmacol. Biochem. Behav. 19:635–644.

    Google Scholar 

  26. Rebec, G. V., Alloway, K. D., andCurtis, S. D. 1981. Apparent serotonergic modulation of the dose-dependent biphasic response of neostriatal neurons produced by damphetamine. Brain Res. 210:277–289.

    Google Scholar 

  27. Reiter, L. W., Anderson, G. E., Laskey, J. W., andCahill, D. F. 1975. Development and behavioral changes in the rat during chronic exposure to lead. Environ. Hlth. Perspec. 12:119–123.

    Google Scholar 

  28. Silbergeld, E. K., andGoldberg, A. M. 1974. Lead-induced behavioral dysfunction: an animal model of hyperactivity. Exp. Neurol. 42:146–157.

    Google Scholar 

  29. Silbergeld, E. K. 1982. Neurochemical and ionic mechanisms of lead neurotoxicity. Pages 1–23,in Prasad, K. N., andVernadakis, A. (eds.) Mechanisms of action of neurotoxic substances, Raven Press, New York.

    Google Scholar 

  30. Sobotka, T. J., andCook, M. P. Postnatal lead acetate exposure in rats: Possible relationship to minimal brain dysfunction. Amer. J. Ment. Defic. 79:5–9.

  31. Walters, J. R., andRoth, R. H. 1976. Dopaminergic neurons—alteration in the sensitivity of tyrosine hydroxylase to inhibition by endogenous dopamine after cessation of impulse flow. Biochem. Pharmacol. 25:649–654.

    Google Scholar 

  32. Walters, J. R., Lanthorn, T. H., Waszczak, B. L., Baring, M. D., Knight, M., andSteardo, L. 1984. Modulation of midbrain dopamine cell activity. Pages 343–351,in Usdin, E., Carlsson, A., Dahlstrom, A., andEngel, J. (eds.), Catecholamines: Neuropharmacology and central nervous system—theoretical aspects, Alan R. Liss, New York.

    Google Scholar 

  33. Wince, L. C., Donovan, C. A., andAzzaro, A. J. 1980. Alterations in the biochemical properties of central dopamine synapses following chronic postnatal PbCO3 exposure. J. Pharmacol. Exp. Ther. 214:642–650.

    Google Scholar 

  34. Zenick, H., andGoldsmith, M. 1981. Drug discrimination learning in lead-exposed rats. Science 212:569–571.

    Google Scholar 

  35. Zenick, H., Lasley, S. M., Greenland, R. D., Caruso, V., Succop, P., Price, D., andMichaelson, I. A. 1982. Regional brain distribution of d-amphetamine in leadexposed rats. Toxicol. Appl. Pharmacol. 64:52–63.

    Google Scholar 

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Author notes

  1. Stephen M. Lasley

    Present address: Department of Pharmacology, Texas College of Osteopathic Medicine, Camp Bowie at Montgomery, 76107, Fort Worth, TX

Authors and Affiliations

  1. Division of Toxicology Department of Environmental Health, University of Cincinnati College of Medicine, 45267, Cincinnati, Ohio

    Stephen M. Lasley, Robert D. Greenland, Daniel J. Minnema & I. Arthur Michaelson

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  1. Stephen M. Lasley
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  2. Robert D. Greenland
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  3. Daniel J. Minnema
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  4. I. Arthur Michaelson
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Lasley, S.M., Greenland, R.D., Minnema, D.J. et al. Altered central monoamine response tod-amphetamine in rats chronically exposed to inorganic lead. Neurochem Res 10, 933–944 (1985). https://doi.org/10.1007/BF00964630

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