| Abstrakt: |
The present study was undertaken to compare the acute and long-term effects of escitalopram and citalopram on rat brain 5-HT neurotransmission, using electrophysiological techniques. In hippocampus, after 2 weeks of treatment with escitalopram (10 mg/kg/day, s.c.) or citalopram (20 mg/kg/day, s.c.), the administration of the selective 5-HT1A receptor antagonist WAY-100,635 (20-100 µg/kg, i.v.) dose-dependently induced a similar increase in the firing activity of dorsal hippocampus CA3 pyramidal neurons, thus revealing direct functional evidence of an enhanced tonic activation of postsynaptic 5-HT1A receptors. In dorsal raphe nucleus, escitalopram was four times more potent than citalopram in suppressing the firing activity of presumed 5-HT neurons (ED50 = 58 and 254 µg/kg, i.v., respectively). Interestingly, the suppressant effect of escitalopram (100 µg/kg, i.v.) was significantly prevented, but not reversed by R-citalopram (250 µg/kg, i.v.). Sustained administration of escitalopram and citalopram significantly decreased the spontaneous firing activity of presumed 5-HT neurons. This firing activity returned to control rate after 2 weeks in rats treated with escitalopram, but only after 3 weeks using citalopram, and was associated with a desensitization of somatodendritic 5-HT1A autoreceptors. These results suggest that the time course of the gradual return of presumed 5-HT neuronal firing activity, which was reported to account for the delayed effect of SSRI on 5-HT transmission, is congruent with the earlier onset of action of escitalopram vs citalopram in validated animal models of depression and anxiety. [ABSTRACT FROM AUTHOR] |
