Abstract
Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum were studied. Repeated administration of citalopram increased the amount of dopamine D2 receptors, the level of dopamine D2 receptor mRNA, and the transcription rate of the dopamine D2 receptor gene. Single administration of citalopram also increased the level of dopamine D2 receptor mRNA with a maximum effect in 2–4 h after the treatment, and the transcription rate of the dopamine D2 receptor gene. The administration of 5-hydroxytryptophan (5-HTP) also increased the level of dopamine D2 receptor mRNA. These results suggest that the increase in the dopamine D2 receptor expression induced by citalopram may be owing, at least partially, to the stimulation of the dopamine D2 receptor gene transcription, and that serotonin (5-HT) may mediate the effects of citalopram in the induction of dopamine D2 receptor expression.
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Ainsworth K., Smith S. E., Zetterström T. S. C., Pei Q., Franklin M., and Sharp T. (1998) Effects of antidepressant drugs on D1 and D2 receptor expression and dopamine release in the nucleus accumbence of the rat. Psychopharmacology 140, 470–477.
Arnt J., Overø K. F., Hyttel J., and Olsen R. (1984) Changes in rat dopamine- and serotonin function in vivo after prolonged administration of the specific 5-HT uptake inhibitor, citalopram. Psychopharmacology 84, 457–465.
Barker E. L. and Blakely R. D. (1995) Norepinephrine and serotonin transporters molecular targets of antidepressant drugs, in Psychopharmacology (Bloom, F. E. and Kupfer, D. J., eds.), Raven, New York, pp. 321–333.
Brunello N., Barbaccia M. L., Chuang D. M., and Costa E. (1982) Down-regulation of β-adrenergic receptors following repeated injections of desmethy limipramine: permissive role of serotonergic axons. Neuropharmacol. 21, 1145–1149.
Bunzow J. R., Van Tol H. H. M., Grandy D. K., Albert P., Salon J., Christie M., et al. (1988) Cloning and expression of a rat D2 dopamine receptor cDNA. Nature 336, 783–787.
Dewar K. M., Soghomonian J.-J., Bruno J. P., Descarries L., and Reader T. A. (1990) Elevation of dopamine D2 but not D1 receptors in adult rat neostriatum after neonatal 6-hydroxydopamine denervation. Brain Res. 536, 287–296.
Dziedzicka-Wasylewska M., Rogoż R., Klimek V., and Maj J. (1997) Repeated administration of antidepressant drugs affects the levels of mRNA coding for D1 and D2 dopamine receptors in the rat brain. J. Neural. Transm. 104, 515–524.
Farooqui S. M., Prasad C., and Ali M. (1992) Production and characterization of a monoclonal antibody to dopamine D2 receptor: comparison with a polyclonal antibody to a different epitope. Biochem. Biophys. Res. Commun. 184, 661–667.
Gundlah C., Hjorth S., and Auerbach S. B. (1997) Autoreceptor antagonists enhance the effect of the reuptake inhibitor citalopram on extracellular 5-HT: this effect persists after repeated citalopram treatment. Neuropharmacology 36, 475–482.
Hjorth S., Westlin D., and Bengtsson H. J. (1977) Way100635-induced augmentation of the 5-HT-elevating action of citalopram: relative importance of the dose of the 5-HT1A (auto)receptor blocker versus that of the 5-HT reuptake inhibitor. Neuropharmacology 36, 461–465.
Hughes Z. A. and Stanford S. C. (1998) Evidence from microdialysis and synaptosomal studies of rat cortex for noradrenaline uptake sites with different sensitivities to SSRIs. Br. J. Pharmacol. 124, 1141–1148.
Hyttel J. (1977) Neurochemical characterization of a new potent and selective serotonin uptake inhibitor: Lu 10-171. Psychopharmacology 51, 225–233.
Hyttel J. (1982) Citalopram-pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Prog. Neuropsychopharmacol. Biol. Psychiatry 6, 277–295.
Hyttel J., Overø K. F., and Arnt J. (1984) Biochemical effects and drug levels in rats after long-term treatment with the specific 5-HT-uptake inhibitor, citalopram. Psychopharmacology 83, 20–27.
Invernizzi R., Bramante M., and Samanin R. (1995) Extracellular concentration of serotonin in the dorsal hippocampus after acute and chronic treatment with citalopram. Brain Res. 696, 62–66.
Invernizzi R., Velasco C., Bramante M., Longo A., and Samanin R. (1997) Effects of 5-HT1A receptor antagonists on citalopram-induced increase in extracellular serotonin in frontal cortex, striatum and dorsal hippocampus. Neuropharmacology 36, 467–473.
Janowsky A., Okada F., Manier D. H., Applegate C. D., Sulser F., and Steranka L. R. (1982) Role of serotonergic input in the regulation of the β-adrenergic receptor-coupled adenylate cyclase system. Science 218, 900,901.
Kameda K. (1995) Thyroid hormone inhibits fatty acid synthase gene transcription in chicken liver. Mol. Cell. Biochem. 144, 105–108.
Klimek V. and Nielsen M. (1987) Chronic treatment with antidepressants decreases the number of [3H]SCH23390 binding sites in the rat striatum and limbic system. Eur. J. Pharmacol. 139, 163–169.
Koe B. K., Weissman A., Welch W. M., and Browne R. G. (1983) Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin. J. Pharmacol. Exp. Ther. 226, 686–700.
Maj J., Rogóż Z., Skuza G., and Sowinska H. (1984) Repeated treatment with antidepressant drugs increases the behavioral response to apmorphine. J. Neural Transm. 60, 273–282.
Maj J., Dziedzicka-Wasylewska M., Rogoż R., Rogóż Z, and Skuza, G. (1996) Antidepressant drugs given repeatedly change the binding of the dopamine D2 receptor agonist, [3H]N-0437, to dopamine D2 receptor in the rat striatum. Eur. J. Pharmacol. 304, 49–54.
Matsubara S., Matsubara R., Kusumi I., Koyama T., and Yamasita I. (1993) Dopamine D1, D2, and serotonin2 receptor occupation by typical and atypical antipsychotic drugs in vitro. J. Pharmacol. Exp. Ther. 265, 498–508.
Mitchell P. J. and Tjian R. (1989) Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science 245, 371–378.
Moret C. and Briley M. (1996) Effects of acute and repeated administration of citalopram on extracellular levels of serotonin in rat brain. Eur. J. Pharmacol. 295, 189–197.
Okada F., Saito Y., Fujieda T., and Yamasita I. (1972) Monoamine changes in the brain of rats injected with L-5-hydroxytryptophan. Nature 238, 355, 356.
Peterson B. and Mørk A. (1996) Chronic treatment with citalopram induces noradrenaline receptor hypoactivity. A microdialysis study. Eur. J. Pharmacol. 300, 67–70.
Prywes R. and Roeder R. G. (1986) Inducible binding of a factor to the c-fos enhancer. Cell 47, 777–784.
Ramamoorthy S., Bauman A. L., Moore K. R., Han H., Yang Feng T., Chang A. S., et al. (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc. Natl. Acad. Sci. USA 90, 2542–2546.
Sakata M., Farooqui S. M., and Prasad C. (1992) Post-transcriptional regulation of loss of rat striatal D2 dopamine receptor during aging. Brain Res. 575, 309–314.
Seeman P. (1995) Dopamine receptors: clinical correlates, in Psychopharmacology (Bloom, F. E. and Kupfer, D. J., eds.), Raven, New York, pp. 295–302.
Seo H., Yang C., Kim H. S., and Kim K. S. (1996) Multiple protein factors interact with the cisregulatory elements of the proximal promoter in a cell-specific manner and regulate transcription of the dopamine β-hydroxylase gene. J. Neurosci. 16, 4102–4112.
Thomas D. R., Nelson D. R., and Johnson A. M. (1987) Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology 93, 193–200.
Thorre K., Ebinger G., and Michotte Y. (1998) 5-HT4 receptor involvement in the serotonin-enhanced dopamine efflux from the substantia nigra of the freely moving rat: a microdialysis study. Brain Res. 796, 117–124.
Tso J. Y., Sun X.-H., Kao T.-h., Reece K. S., and Wu R. (1985) Isolation and characterization of rat human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acid Res. 13, 2485–2502.
Valdenaire O., Vernier P., Maus M., Dumas Milne Edwards J.-B., and Mallet J. (1994) Transcription of the dopamine-D2-receptor gene from two promoters. Eur. J. Biochem. 220, 577–584.
Willner P. (1995) Dopaminergic mechanism in depression and mania, in Psychopharmacology (Bloom F. E. and Kupfer D. J., eds.), Raven, New York, pp. 921–931.
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Kameda, K., Kusumi, I., Suzuki, K. et al. Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum. J Mol Neurosci 14, 77–86 (2000). https://doi.org/10.1385/JMN:14:1-2:077
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DOI: https://doi.org/10.1385/JMN:14:1-2:077