Details

Autor(en) / Beteiligte

• 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

Titel

Serotonin4 (5-HT4) Receptor Agonists Are Putative Antidepressants with a Rapid Onset of Action

Ist Teil von

• Neuron (Cambridge, Mass.), 2007-09, Vol.55 (5), p.712-725

Ort / Verlag

Cambridge: Elsevier Limited

Erscheinungsjahr

2007

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Current antidepressants are clinically effective only after several weeks of administration. Here, we show that serotonin4(5-HT4) 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-HT1Aautoreceptors, increased tonus on hippocampal postsynaptic 5-HT1Areceptors, 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-HT4agonist 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-HT4receptor agonists as a putative class of antidepressants with a rapid onset of action.