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Effects of acute and subacute cocaine administration on the CNS dopaminergic system in Wistar-Kyoto and spontaneously hypertensive rats: III. Dopamine uptake

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Abstract

The characteristics of dopamine uptake after acute and subacute cocaine administration were determined in striata from WKY and SHR. In acutely-treated (40 mg/kg, s.c.) rats, significant increases in the Vmax of dopamine uptake were observed 30 min after the cocaine injection in both strains, without changes in Km values. The in vitro IC50 for cocaine was significantly decreased at 30 min in WKY and at 2 h in SHR. However, the in vitro IC50 for GBR-12909 was significantly increased at 30 min and at 2 h in both strains following cocaine administration. In both strains, the density (Bmax) of the [3H]GBR-12935 binding site was significantly increased at 30 min and at 2 h with no charges in Kd. In subacutely-treated (20 mg/kg, twice daily for 3 or 7 days) rats, a significant increase in the Km for dopamine uptake was observed in 7 day treated SHR. The in vitro IC50 for GBR-12909 was significantly increased in 3 day treated WKY. The results suggest that cocaine administration alters dopamine uptake and characteristics of dopamine uptake sites in the rat brain.

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References

  1. Dackis, C. A., and M. S. Gold 1985. New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci. Biochem. Rev. 9:469–477.

    Google Scholar 

  2. Bhargava, H. N. 1984. Effect of cyclo (leucyl-glycine) on [3H]spiroperidol binding in the corpus striatum and hypothalamus of spontaneously hypertensive rats. Eur. J. Pharmacol. 100:109–112.

    Google Scholar 

  3. Chiu, P., Rajakumar, G., Chiu, S., Kwan, C-Y., and R. K. Mishra. 1982. Enhanced [3H]spiroperidol binding in striatum of spontaneously hypertensive rat (SHR). Eur. J. Pharmacol. 82:243–244.

    Google Scholar 

  4. Le Fur, G., Guilloux, F., Kabouche, M., Mitrani, N., Ferris, O., and A. Uzan. 1981. Central dopaminergic neurons during development of genetic and DOCA-salt hypertension in the rat. Dev. Brain Res. 1:153–163.

    Google Scholar 

  5. Le Fur, G., Guilloux, F., and A. Uzan. 1983. Evidence for an increase in [3H]spiperone binding in hypothalamic nuclei during the development of spontaneous hypertension in the rat. Clin. Exp. Hyperten. A5:1537–1542.

    Google Scholar 

  6. Lim, D. K., Ito, Y., Hoskins, B., Rockhold, R. W., and I. K. Ho. 1989. Comparative studies of muscarinic and dopamine receptors in three strains of rat. Eur. J. Pharmacol. 165:279–287.

    Google Scholar 

  7. Myers, M. M., Whittemore, S. R., and E. D. Hendley. 1981. Changes in catecholamine neuronal uptake and receptor binding in the brains of spontaneously hypertensive rats. Brain Res. 220:325–338.

    Google Scholar 

  8. Van Den Buuse, M., and W. De Jong. 1989. Differential effects of dopaminergic drugs on open-field behavior of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. J. Pharmacol. Exp. Ther. 248:1189–1196.

    Google Scholar 

  9. Bonnett, J. J., and J. Costentin. 1986. GBR 12783, a potent and selective inhibitor of dopamine uptake: biochemical studies in vivo and ex vivo. Eur. J. Pharmacol. 12:199–209.

    Google Scholar 

  10. Heikkila, R. E., and L. Manzino. 1984. Behavioral properties of GBR 12909, GBR 13069 and GBR 13098: Specific inhibitors of dopamine uptake. Eur. J. Pharmacol. 103:241–248.

    Google Scholar 

  11. Andersen, P. H. 1987. Biochemical and pharmacological characterization of GBR 12935 binding in vitro to rat striatal membranes: labelling of the dopamine uptake complex. J. Neurochem. 48:1887–1896.

    Google Scholar 

  12. Glowinski, J., and L. L. Iversen. 1966. Regional studies of catecholamines in the rat brain-I. The disposition of3H-norepinephrine,3H-dopamine and3H-DOPA in various regions of the rat. J. Neurochem. 13:655–669.

    Google Scholar 

  13. Haberland, N., and L. Hetey. 1987. Studies in postmortem dopamine uptake 1. Kinetic characterization of the synaptosomal dopamine uptake in rat and human brain after postmortem storage and cryopreservation. Comparison with noradrenaline and serotonin uptake. J. Neural Trans. 68:289–301.

    Google Scholar 

  14. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and R. J. Randall. 1951. Protein measurement with Folin phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  15. Munson, P. J., and D. Rodbard. 1980. A versatile computerized approach for the characterization of ligand binding systems. Anal. Biochem. 107:220–239.

    Google Scholar 

  16. Iversen, L. L. 1974. Uptake mechanisms of neurotransmitter amines. Biochem. Pharmacol. 23:1927–1935.

    Google Scholar 

  17. Parenti, M., Flauto, C., Poarati, E. Vescovi, A., and Groppetti, A. 1986. Differential effect of repeated treatment with L-DOPA on dopamine D-1 or D-2 receptors. Neuropharmacol. 25:331–334.

    Google Scholar 

  18. Missale, C., Castelletti, L., Govoni, S., Spano, P. F., Trabucchi, M., and I. Hanbauer. 1985. Dopamine uptake is differentially regulated in rat striatum and nucleus accumbens. J. Neurochem. 45:51–56.

    Google Scholar 

  19. Near, J. A., Bigelow, J. C., and R. M. Wightman. 1988. Comparison of uptake of dopamine in rat striatal chopped tissue and synaptosomes. J. Pharmacol. Exp. Ther. 245:921–927.

    Google Scholar 

  20. Hadfield, M. G., and E. A. Nugent. 1983. Cocaine: comparative effect on dopamine uptake in extrapyramidal and limbic systems. Biochem. Pharmacol. 32:744–746.

    Google Scholar 

  21. Nicolaysen, L. C., Pan, H-T., and J. B. Justice Jr. 1988. Extracellular cocaine and dopamine concentrations are linearly related in rat striatum. Brain Res. 456:317–323.

    Google Scholar 

  22. Tuomisto, J., and L. O. Tuomisto. 1987. Comformationally rigid dopamine analogues as inhibitors of dopamine and 5-hydroxytryptamine uptake by synaptosomes. J. Neural Trans. 68:191–196.

    Google Scholar 

  23. Altar, C. A., and J. F. Marshall. 1988. Neostriatal dopamine uptake and reversal of age-related movement disorders with dopamine uptake inhibitors. Ann. NY Acad. Sci. 515:343–354.

    Google Scholar 

  24. Change, G. D., and V. D. Ramirez. 1989. Studies of the in vitro catabolism of exogenous dopamine as infused through a push-pull cannula implanted in the rat caudate nucleus. Brain Res. 481:265–273.

    Google Scholar 

  25. Sershen, H., Reith, M. E. A., Hashim, A., and A. Lajtha. 1984. Reduction of dopamine uptake and cocaine binding in mouse striatum by N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Eur. J. Pharmacol. 102:175–178.

    Google Scholar 

  26. Calligaro, D. O., and M. E. Eldefrawi. 1988. High-affinity stereospecific binding of [3H]cocaine in striatum and its relationship to the dopamine transporter. Mem. Biochem. 7:87–106.

    Google Scholar 

  27. Galloway, M. P. 1988. Neurochemical interactions of cocaine with dopaminergic systems. Trend. Pharmacol. Sci. 9:451–454.

    Google Scholar 

  28. Kennedy, L. T., and I. Hanbauer. 1983. Sodium-sensitive cocaine binding to rat striatal membranes: possible relationship to dopamine uptake sites. J. Neurochem. 41:172–178.

    Google Scholar 

  29. Tsuda, K., Tsuda, S., and Y. Masuyama. 1988. The role of dopamine in the regulation of neurotransmitter release in spontaneously hypertensive rats. Jpn. Heart. J. 29:215–222.

    Google Scholar 

  30. Van Den Buuse, M., Versteeg, D. H. G., and W. De Jong. 1986. Brain dopamine depletion by lesions in the substantia nigra attenuates the development of hypertension in the spontaneously hypertensive rat. Brain Res. 365:69–78.

    Google Scholar 

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Lim, D.K., Yu, Z.J., Hoskins, B. et al. Effects of acute and subacute cocaine administration on the CNS dopaminergic system in Wistar-Kyoto and spontaneously hypertensive rats: III. Dopamine uptake. Neurochem Res 15, 629–634 (1990). https://doi.org/10.1007/BF00973754

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