Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration

Abstract

Objectives: 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.