Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration.
OBJECTIVE
The aim of this study was to investigate the acute modulation of the neurotrophin Brain-derived neurotrophic factor (BDNF) by the novel antidepressant agomelatine and the relative contribution of its melatonergic and serotonergic receptor components.


METHODS
BDNF mRNA levels were measured in rat hippocampus and prefrontal cortex after acute administration of agomelatine, melatonin or the 5-HT(2C) antagonist S32006.


RESULTS
BDNF expression was significantly increased 16 h after acute agomelatine administration, an effect that follows a specific temporal profile, is limited to the prefrontal cortex and it is due to changes of specific neurotrophin transcripts. Moreover, the acute up-regulation of BDNF mRNA levels appears to be the result of a synergistic effect between the melatonergic properties of agomelatine as MT1/MT2 agonist and its serotonergic 5-HT(2C) antagonism, since either melatonin or the 5-HT(2C) antagonist S32006 does not mimic the effects of agomelatine.


CONCLUSIONS
These data provide evidence that acute agomelatine treatment modulates the expression of BDNF through a functional interaction between melatonergic MT1/MT2 and serotonergic 5-HT(2C) receptors, supporting the notion that intracellular events can be regulated via a synergistic activity of different neuromodulatory systems.
Molteni
Raffaella
R
Center of Neuropharmacology, Department of Pharmacological Sciences, Universita' degli Studi di Milano, Milan, Italy.
Calabrese
Francesca
F
Pisoni
Sara
S
Gabriel
Cecilia
C
Mocaer
Elisabeth
E
Racagni
Giorgio
G
Riva
Marco A
MA
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis*; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000737:chemistry* / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044094:Receptors, Melatonin / Q000187:drug effects / Q000502:physiology; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D009281:Naphthalenes
D000081:Acetamides; D019208:Brain-Derived Neurotrophic Factor; D006993:Hypnotics and Sedatives; D007211:Indoles; D008550:Melatonin; D011725:Pyridines; D012333:RNA, Messenger; D044094:Receptors, Melatonin; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; C533966:S32006; C084711:agomelatine; D009281:Naphthalenes