Abstract
In vivo effects of chronic lithium administration on dopaminergic and serotonergic receptor binding were studied in the striatum and cerebral cortex of the rat. [3H]Domperidone was used as the ligand for the dopaminergic receptor, and [3H]ketanserin for the serotonergic system. Long-term ingestion of lithium (2–3 months) resulted in high levels of lithium in the cerebral cortex and significantly higher potassium levels; the sodium content remained at normal levels. The kinetic constants (K d andB max) of [3H]domperidone binding sites measured in the striatum did not show any deviation from control values, but the receptor concentration (B max) of [3H]ketanserin binding sites was significantly reduced in the cerebral cortex of lithium-treated rats. The apparent dissociation constant (K d) was not changed. The results indicate that the serotonergic component of the [3H]spiperone binding site, which we had previously found to be affected by chronic lithium treatment and which was shown by Peroutka and Snyder (1) to be the 5-HT2 receptor, is selectively affected by lithium.
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References
Peroutka, S. J., andSnyder, S. H. 1979. Multiple serotonin receptors: differential binding of [3H]hydroxytryptamine, [3H]lysergic acid and [3H]spiroperidol. Mol. Pharmacol. 16:687–699.
Coppen, A. 1973. The role of lithium carbonate in the treatment and prophylaxis of the affective disorders. Biochem. Soc. Trans. 1:74.
Wajda, I. J., Banay-Schwartz, M., Manigault, I., andLajtha, A. 1981. Effect of lithium and sodium ions on opiate- and dopamine-receptor binding. Neurochem. Res. 6:321–331.
Banay-Schwartz, M., Wajda, I. J., Manigault, I., DeGuzman, T., andLajtha, A. 1982. Lithium: Effect on [3H]spiperone binding, ionic content, and amino acid levels in the brain of rats. Neurochem. Res. 7:179–189.
Wajda, I. J., Banay-Schwartz, M., DeGuzman, T., andManigault, I. 1983. Dietary lithium during development. Neurochem. Res. 8:637–648.
Near, I. J., andMahler, H. R. 1981. Dopamine receptor in subcellular fractions from bovine caudate: Enrichment of [3H]spiperone binding in a postsynaptic membrane fraction. J. Neurochem. 36:1142–1151.
Howlett, D. R., andNahorski, S. R. 1980. Quantitative assessment of heterogeneous [3H]spiperone binding to rat neostriatum and frontal cortex. Life Sci. 26:511–517.
Leysen, J. E., Niemegeers, C. J. E., Tellneare, J. P., andLaduron, P. M. 1978. Serotonergic component of neuroleptic receptor. Nature (London) 272:168–171.
Pedigo, N. W., Reisine, T. D., Fields, J. Z., andYamamura, H. J. 1978. [3H]Spiroperidol binding to two receptor sites in both corpus striatum and cerebral cortex of rat brain. Eur. J. Pharmacol. 50:451–453.
Rosenblatt, J. E., Pert, A., Layton, B., andBunney, W. E. Jr. 1980. Chronic lithium reduces [3H]spiroperidol binding in the striatum. Eur. J. Pharmacol. 67:321–322.
Lazareno, S., andNahorski, S. R. 1982. Selective labeling of dopamine (D2) receptors in rat striatum by [3H]domperidone but not by [3H]spiperone. Eur. J. Pharmacol. 81:273–285.
Leysen, J. F., Niemegeers, C. J. E., VanNeuten, J. M., andLaduron, P. M. 1982. [3H]Ketanserin (R 41468), a selective3H-ligand for serotonin receptor. Mol. Pharmacol. 21:301–314.
Lowry, O. H., Rosebrough, N. J., Farr, L. A., andRandall, R. J. 1951. Protein measurement in the Folin phenol reagent. J. Biol. Chem. 193:265–275.
Leysen, J. E., Awouters, F., Kennis, L., Laduron, P. M., Vandenberg, J., andJansen, P. A. Y. 1981. Receptor binding profile of R 41468, a novel antagonist at 5-HT2receptors. Life Sci. 28:1015–1022.
Laduron, P. M., andLeysen, J. E. 1979. Domperidone, a specific in vitro dopamine antagonist, devoid of in vivo central dopaminergic activity. Biochem. Pharmacol. 28:2161–2165.
Greese, J., Sibley, D. R., andLeff, S. A. 1984. Agonist interaction with dopamine receptors; focus on radioligand binding studies. Fed. Proc. 34:2779–2784.
Tamimoto, K., Maeda, K., andTeradre, T. 1983. Inhibitory effect of lithium on neuroleptic and serotonin receptors in rat brain. Brain Res. 265:145–151.
Staunton, D. A., Magistretti, P. J., Shoemaker, W. J., Deyo, D. M.. andBloom, F. E. 1982. Effect of chronic lithium-treatment on dopamine receptors in the rat corpus striatum. Brain Res. 232:401–412.
Reeches, A., Wagner, H. R., Jackson, V., andFahn, S. 1982. Chronic lithium administration has no effect on haloperidol-induced supersensitivity of pre- and postsynaptic dopamine receptors in rat brain. Brain Res. 246:172–176.
Treiser, S. L., Cascio, C. S., O'Donohue, T. L., Thoa, N. B., Jacobowitz, D. M., andKellar, K. J. 1981. Lithium increases serotonin release and decreases serotonin receptor in hippocampus. Science 213:1529–1531.
Maggi, A., andEnna, S. J. 1980. Regional alterations in rat brain neurotransmitter systems following lithium treatment. J. Neurochem. 34:888–892.
Fisher, S., andDe Robertis, E. 1969. Subcellular distribution and chemical nature of the receptor for 5-hydroxytryptamine in the central nervous system. J. Neurochem. 16:1201–1209.
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Special Issue dedicated to Prof. Eduardo De Robertis.
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Wajda, I.J., Banay-Schwartz, M., Manigault, I. et al. Modulation of the serotonin S2-receptor in brain after chronic lithium. Neurochem Res 11, 949–957 (1986). https://doi.org/10.1007/BF00965585
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DOI: https://doi.org/10.1007/BF00965585