EFFECTS OF CHRONIC TREATMENT WITH FLUOXETINE AND CITALOPRAM ON 5-HT UPTAKE, 5-HT1B AUTORECEPTORS, 5-HT3 AND 5-HT4 RECEPTORS IN RATS

The effect in rats of chronic treatment with two specific 5-HT reuptak e inhibitors (SSRI) with anti-depressant 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 o n some mechanisms involved in central 5-HT neurotransmission. No adapt ive modifications of brain 5-HT uptake (sites) were found by measuring functional [H-3]5-MT uptake and [H-3]citalopram binding in cortical a nd hippocampal synaptosomes, and by [H-3]citalopram binding autoradiog raphy in the raphe nuclei (5-HT cell bodies) and the ventral tegmental area (5-HT axonal pathway). Chronic treatments had no effect on presy naptic 5-HT1B autoreceptors, functionally evaluated by measuring 5-HT1 B-mediated inhibition of depolarization-induced [H-3]5-HT release from cortical and hippocampal synaptosomes. Chronic citalopram or fluoxeti ne did not significantly affect the binding of [3H]BRL-43694 to 5-HT3 receptors in the rat brain cortex. Citalopram had no effect on [(125)] SB-207710 binding to 5-HT4 receptors, measured by autoradiography in t he substantia nigra. Negative results, such as those reported in the p resent study, could be due to a number of variables including the anim al 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 br ain 5-HT transporters, terminal 5-HT1B receptors, 5-HT3 and 5-HT4 rece ptors may not be a general effect induced by all SSRI.