Effects of chronic treatment with fluoxetine and citalopram on 5-HT uptake, 5-HT(1B) autoreceptors, 5-HT3 and 5-HT4 receptors in rats

Marco Gobbi, Daniela Crespi, Maria Cristina Foddi, Claudia Fracasso, Laura Mancini, Luca Parotti, Tiziana Mennini

Research output: Contribution to journalArticle

Abstract

The effect in rats of chronic treatment with two specific 5-HT reuptake inhibitors (SSRI) with antidepressant properties, citalopram (10 mg/kg, i.p. twice a day for 14 days, one day washout) and fluoxetine (15 mg/kg, p.o. twice a day for 21 days, 7 days washout), was evaluated on some mechanisms involved in central 5-HT neurotransmission. No adaptive modifications of brain 5-HT uptake (sites) were found by measuring functional [3H]5-HT uptake and [3H]citalopram binding in cortical and hippocampal synaptosomes, and by [3H]citalopram binding autoradiography in the raphe nuclei (5-HT cell bodies) and the ventral tegmental area (5-HT axonal pathway). Chronic treatments had no effect on presynaptic 5-HT(1B) autoreceptors, functionally evaluated by measuring 5-HT(1B)-mediated inhibition of depolarization-induced [3H]5-HT release from cortical and hippocampal synaptosomes. Chronic citalopram or fluoxetine did not significantly affect the binding of [3H]BRL-43694 to 5-HT3 receptors in the rat brain cortex. Citalopram had no effect on [125I]SB-207710 binding to 5-HT4 receptors, measured by autoradiography in the substantia nigra. Negative results, such as those reported in the present study, could be due to a number of variables including the animal species, the treatment schedule or the brain areas considered, thus explaining the differences from some previous reports of significant effects of SSRI. However, our negative data are in agreement with many other published studies, suggesting that adaptive modifications of brain 5-HT transporters, terminal 5-HT(1B) receptors, 5-HT3 and 5-HT4 receptors may not be a general effect induced by all SSRI.

Original languageEnglish
Pages (from-to)22-28
Number of pages7
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume356
Issue number1
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Pharmacology

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