Effects of Acute and Long-Term Administration of Escitalopram and Citalopram on Serotonin Neurotransmission: an In Vivo Electrophysiological Study in Rat Brain

Abstract

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-HT 1A receptor antagonist WAY-100,635 (20-100 mg/kg, i.v.) dose-dependently induced a similar increase in the firing activity of dorsal hippocampus CA 3 pyramidal neurons, thus revealing direct functional evidence of an enhanced tonic activation of postsynaptic 5-HT 1A receptors. In dorsal raphe nucleus, escitalopram was four times more potent than citalopram in suppressing the firing activity of presumed 5-HT neurons (ED 50 ¼ 58 and 254 mg/kg, i.v., respectively). Interestingly, the suppressant effect of escitalopram (100 mg/kg, i.v.) was significantly prevented, but not reversed by R-citalopram (250 mg/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-HT 1A 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.

Pharmacological Blockade of 5-HT7 Receptors as a Putative Fast Acting Antidepressant Strategy

“…In fact, this enhancement was shown by the manifestation of an enhanced inhibitory tone on postsynaptic 5-HT 1A receptors, as the selective antagonist WAY 100 635 was able to increase CA3 pyramidal neuron activity (Figure 4). Such an effect was reported using classical ADs after 2 to 3 weeks of treatment (Haddjeri et al, 1998b;Besson et al, 2000;El Mansari et al, 2005, Lucas et al, 2007. However, it was observed that fluoxetine was also effective after a 1-week treatment.…”

Acute and chronic effects of citalopram on 5‐HT1A receptor—Labeling by [18F]MPPF and—Coupling to receptors‐G proteins

“…In particular, enhanced 5-HT-mediated inhibitory potentials in FCx (Bobula et al, 2003b) and attenuated glutamatergic synaptic transmission (Bobula et al, 2003a) were observed after a 14-day treatment with citalopram and desipramine, respectively. Similarly, chronic citalopram treatment induced an enhanced tonic activation of postsynaptic 5-HT 1A receptors in hippocampus (El Mansari et al, 2005).…”

Acute escitalopram treatment inhibits REM sleep rebound and activation of MCH-expressing neurons in the lateral hypothalamus after long term selective REM sleep deprivation

“…All these effects were also demonstrated in rodents (Monaca et al 2003;Vas et al 2013). The main mechanisms existing in the background of REMS suppression of SSRIs imply the increase in serotonin (5-HT) concentration via the inhibition of its reuptake and the concomitant activation of postsynaptic 5-HT 1A and 5-HT 1B receptors (El Mansari et al 2005;Maudhuit et al 1996).…”