Serotonin(4) (5-HT(4)) Receptor Agonists Are Putative
Antidepressants with a Rapid Onset of Action
by
Lucas G, Rymar VV, Du J, Mnie-Filali O, Bisgaard C, Manta S, Lambas-Senas L,
Wiborg O, Haddjeri N, Piñeyro G, Sadikot AF, Debonnel G.
Université McGill, Département de Psychiatrie,
Bâtiment de Recherche et de Formation,
Bureau 207, 1033 Avenue des Pins Ouest,
Montréal, QC, H3A 1A1 Canada;
Centre de Recherche Fernand Séguin,
Université de Montréal,
Montréal, QC, H1N 3V2 Canada.
Neuron. 2007 Sep 6;55(5):712-25.Links

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.

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5-HT7 receptor antagonists as antidepressants

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