Serotonin(4) (5-HT(4)) receptor agonists are putative antidepressants with a rapid onset of action |
| |
Authors: | Lucas Guillaume Rymar Vladimir V Du Jenny Mnie-Filali Ouissame Bisgaard Christina Manta Stella Lambas-Senas Laura Wiborg Ove Haddjeri Nasser Piñeyro Graciela Sadikot Abbas F Debonnel Guy |
| |
Affiliation: | Université McGill, Département de Psychiatrie, Batiment de Recherche et de Formation, Bureau 207, 1033 Avenue des Pins Ouest, Montréal, QC, H3A 1A1 Canada. guillaume.lucas@gmail.com |
| |
Abstract: | Current antidepressants are clinically effective only after several weeks of administration. Here, we show that serotonin(4) (5-HT(4)) agonists reduce immobility in the forced swimming test, displaying an antidepressant potential. Moreover, a 3 day regimen with such compounds modifies rat brain parameters considered to be key markers of antidepressant action, but that are observed only after 2-3 week treatments with classical molecules: desensitization of 5-HT(1A) autoreceptors, increased tonus on hippocampal postsynaptic 5-HT(1A) receptors, and enhanced phosphorylation of the CREB protein and neurogenesis in the hippocampus. In contrast, a 3 day treatment with the SSRI citalopram remains devoid of any effect on these parameters. Finally, a 3 day regimen with the 5-HT(4) agonist RS 67333 was sufficient to reduce both the hyperlocomotion induced by olfactory bulbectomy and the diminution of sucrose intake consecutive to a chronic mild stress. These findings point out 5-HT(4) receptor agonists as a putative class of antidepressants with a rapid onset of action. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|