Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus.
by
Soumier A, Banasr M, Lortet S, Masmejean F, Bernard N, Kerkerian-Le-Goff L,
Gabriel C, Millan MJ, Mocaer E, Daszuta A.
IC2N, IBDML, UMR 6216, Marseille, France.
Neuropsychopharmacology. 2009 Jul 1.

ABSTRACT

Agomelatine is a novel antidepressant acting as a melatonergic receptor agonist and serotonergic (5-HT(2C)) receptor antagonist. In adult rats, chronic agomelatine treatment enhanced cell proliferation and neurogenesis in the ventral hippocampus (VH), a region pertinent to mood disorders. This study compared the effects of agomelatine on cell proliferation, maturation, and survival and investigated the cellular mechanisms underlying these effects. Agomelatine increased the ratio of mature vs immature neurons and enhanced neurite outgrowth of granular cells, suggesting an acceleration of maturation. The influence of agomelatine on maturation and survival was accompanied by a selective increase in the levels of BDNF (brain-derived neurotrophic factor) vs those of VEGF (vascular endothelial factor) and IGF-1 (insulin-like growth factor 1), which were not affected. Agomelatine also activated several cellular signals (extracellular signal-regulated kinase1/2, protein kinase B, and glycogen synthase kinase 3beta) known to be modulated by antidepressants and implicated in the control of proliferation/survival. Furthermore, as agomelatine possesses both melatonergic agonist and serotonergic (5-HT(2C)) antagonist properties, we determined whether melatonin and 5-HT(2C) receptor antagonists similarly influence cell proliferation and survival. Only the 5-HT(2C) receptor antagonists, SB243,213 or S32006, but not melatonin, mimicked the effects of agomelatine on cell proliferation in VH. The promoting effect of agomelatine on survival was not reproduced by the 5-HT(2C) receptor antagonists or melatonin alone. However, it was blocked by a melatonin antagonist, S22153. These results show that agomelatine treatment facilitates all stages of neurogenesis and suggest that a joint effect of melatonin agonism and 5HT(2C) antagonism may be involved in promotion by agomelatine of survival in the hippocampus.

5-HT2c
Valdoxan
Serotonin
Melatonin
Agomelatine
Agomelatine trials
Agomelatine: structure
Serotonin 5-HT2c receptors
Agomelatine (Valdoxan): review
Agomelatine, stress and memory
New antidepressants: agomelatine
Agomelatine (Valdoxan) and melatonergic drugs
Agomelatine (Valdoxan): efficacy and tolerance profile
Agomelatine, 5-HT2c antagonist and melatonin agonist
Agomelatine, circadian rhythms and antidepresant efficacy
Agomelatine (Valdoxan, Melitor, Thymanax) to treat major depression
Agomelatine (Valdoxan) and the serotonin 5-HT2b and 5-HT2c receptors
Jet lag: therapeutic use of melatonin and possible application of melatonin analogs
Insomnia, prolonged-release melatonin & synthetic melatoninergic agonists (i.e. agomelatine)

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