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J Psychiatry Neurosci. 1994 January; 19(1): 63–67.
PMCID: PMC1188564

Effects of repeated treatment with fluoxetine and citalopram, 5-HT uptake inhibitors, on 5-HT1A and 5-HT2 receptors in the rat brain.


Repeated treatment with fluoxetine and citalopram, which are potent 5-HT reuptake inhibitors, resulted in different regulation of 5-HT1A and 5-HT2 receptors in the rat brain. Their effects were compared with those of other antidepressants: imipramine, mianserin and levoprotiline. The density of 5-HT1A receptors, labelled with [3H]8-OH-DPAT, in the rat hippocampus was enhanced after citalopram, imipramine, mianserin and levoprotiline, but not altered after fluoxetine administration. [3H]Ketanserin binding sites, which label 5-HT2 receptors, were increased after fluoxetine and levoprotiline, but decreased after citalopram, imipramine and mianserin in the rat cerebral cortex. Acute administration of fluoxetine, but not citalopram, resulted in a decreased density of 5-HT1A receptors. 5-HT2 receptors were not changed by acute administration of either fluoxetine or citalopram. The obtained results indicate that besides 5-HT reuptake inhibiting properties of both compounds, there may exist an additional mechanism(s) of their action, which leads to different regulation of 5-HT1A and 5-HT2 receptors.

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Selected References

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  • Arnt J, Hyttel J, Overø KF. Prolonged treatment with the specific 5-HT-uptake inhibitor citalopram: effect on dopaminergic and serotonergic functions. Pol J Pharmacol Pharm. 1984 Mar-Jun;36(2-3):221–230. [PubMed]
  • Caldecott-Hazard S, Morgan DG, DeLeon-Jones F, Overstreet DH, Janowsky D. Clinical and biochemical aspects of depressive disorders: II. Transmitter/receptor theories. Synapse. 1991 Dec;9(4):251–301. [PubMed]
  • Cervo L, Samanin R. Potential antidepressant properties of 8-hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin1A receptor agonist. Eur J Pharmacol. 1987 Dec 1;144(2):223–229. [PubMed]
  • Cheetham SC, Crompton MR, Katona CL, Horton RW. Brain 5-HT1 binding sites in depressed suicides. Psychopharmacology (Berl) 1990;102(4):544–548. [PubMed]
  • Conn PJ, Sanders-Bush E. Central serotonin receptors: effector systems, physiological roles and regulation. Psychopharmacology (Berl) 1987;92(3):267–277. [PubMed]
  • de Montigny C, Aghajanian GK. Tricyclic antidepressants: long-term treatment increases responsivity of rat forebrain neurons to serotonin. Science. 1978 Dec 22;202(4374):1303–1306. [PubMed]
  • Goodwin GM, Green AR, Johnson P. 5-HT2 receptor characteristics in frontal cortex and 5-HT2 receptor-mediated head-twitch behaviour following antidepressant treatment to mice. Br J Pharmacol. 1984 Sep;83(1):235–242. [PubMed]
  • Green AR. Evolving concepts on the interactions between antidepressant treatments and monoamine neurotransmitters. Neuropharmacology. 1987 Jul;26(7B):815–822. [PubMed]
  • Green AR, Heal DJ, Johnson P, Laurence BE, Nimgaonkar VL. Antidepressant treatments: effects in rodents on dose-response curves of 5-hydroxytryptamine- and dopamine-mediated behaviours and 5-HT2 receptor number in frontal cortex. Br J Pharmacol. 1983 Oct;80(2):377–385. [PubMed]
  • Kellar KJ, Cascio CS, Butler JA, Kurtzke RN. Differential effects of electroconvulsive shock and antidepressant drugs on serotonin-2 receptors in rat brain. Eur J Pharmacol. 1981 Feb 19;69(4):515–518. [PubMed]
  • Kennett GA, Dourish CT, Curzon G. Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Eur J Pharmacol. 1987 Feb 24;134(3):265–274. [PubMed]
  • Leysen JE. Gaps and peculiarities in 5-HT2 receptor studies. Neuropsychopharmacology. 1990 Oct-Dec;3(5-6):361–369. [PubMed]
  • Leysen JE, Niemegeers CJ, Van Nueten JM, Laduron PM. [3H]Ketanserin (R 41 468), a selective 3H-ligand for serotonin2 receptor binding sites. Binding properties, brain distribution, and functional role. Mol Pharmacol. 1982 Mar;21(2):301–314. [PubMed]
  • Maj J, Moryl E. Effects of sertraline and citalopram given repeatedly on the responsiveness of 5-HT receptor subpopulations. J Neural Transm Gen Sect. 1992;88(2):143–156. [PubMed]
  • Maj J, Moryl E. Effects of fluoxetine given chronically on the responsiveness of 5-HT receptor subpopulations to their agonists. Eur Neuropsychopharmacol. 1993 Jun;3(2):85–94. [PubMed]
  • Mann JJ, Arango V, Marzuk PM, Theccanat S, Reis DJ. Evidence for the 5-HT hypothesis of suicide. A review of post-mortem studies. Br J Psychiatry Suppl. 1989 Dec;(8):7–14. [PubMed]
  • Mogilnicka E, Klimek V. Mianserin, danitracen and amitriptyline withdrawal increases the behavioural responses of rats to L-5-HTP. J Pharm Pharmacol. 1979 Oct;31(10):704–705. [PubMed]
  • Peroutka SJ, Snyder SH. Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Science. 1980 Oct 3;210(4465):88–90. [PubMed]
  • Schlegel JR, Peroutka SJ. Nucleotide interactions with 5-HT1A binding sites directly labeled by [3H]-8-hydroxy-2-(DI-n-propylamino)tetralin ([3H]-8-OH-DPAT). Biochem Pharmacol. 1986 Jun 15;35(12):1943–1949. [PubMed]
  • Tatarczyńska E, Chojnacka-Wójcik E. Effects of 8-OH-DPAT and ipsapirone in the tests used for evaluation of the antidepressant action. Pol J Pharmacol Pharm. 1989 Jul-Aug;41(4):321–330. [PubMed]
  • van Praag HM, Korf J. A pilot study of some kinetic aspects of the metabolism of 5-hydroxytryptamine in depressive patients. Biol Psychiatry. 1971;3(2):105–112. [PubMed]
  • Vetulani J, Lebrecht U, Pilc A. Enhancement of responsiveness of the central serotonergic system and serotonin-2 receptor density in rat frontal cortex by electroconvulsive treatment. Eur J Pharmacol. 1981 Nov 19;76(1):81–85. [PubMed]
  • Welner SA, De Montigny C, Desroches J, Desjardins P, Suranyi-Cadotte BE. Autoradiographic quantification of serotonin1A receptors in rat brain following antidepressant drug treatment. Synapse. 1989;4(4):347–352. [PubMed]
  • Willner P. Antidepressants and serotonergic neurotransmission: an integrative review. Psychopharmacology (Berl) 1985;85(4):387–404. [PubMed]
  • Wong DT, Fuller RW, Robertson DW. Fluoxetine and its two enantiomers as selective serotonin uptake inhibitors. Acta Pharm Nord. 1990;2(3):171–180. [PubMed]
  • Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN. 5HT2 receptor changes in major depression. Biol Psychiatry. 1990 Mar 1;27(5):489–496. [PubMed]

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