Open Access Open Badges Research article

Blockade of stress-induced increase of glutamate release in the rat prefrontal/frontal cortex by agomelatine involves synergy between melatonergic and 5-HT2C receptor-dependent pathways

Daniela Tardito1, Marco Milanese2, Tiziana Bonifacino2, Laura Musazzi1, Massimo Grilli2, Alessandra Mallei1, Elisabeth Mocaer3, Cecilia Gabriel-Gracia3, Giorgio Racagni14, Maurizio Popoli1* and Giambattista Bonanno2

Author Affiliations

1 Center of Neuropharmacology - Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Italy

2 Department of Exp. Medicine, Section of Pharmacology and Toxicology and Center of Excellence for Biomedical Research and National Institute of Neuroscience, University of Genova, Italy

3 IDR Servier, Croissy-sur-Seine, France

4 I.R.C.C.S San Giovanni di Dio - Fatebenefratelli, Brescia, Italy

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BMC Neuroscience 2010, 11:68  doi:10.1186/1471-2202-11-68

Published: 3 June 2010



Agomelatine is a melatonergic receptor agonist and a 5HT2C receptor antagonist that has shown antidepressant efficacy. In order to analyze separately the effect of the two receptorial components, rats were chronically treated with agomelatine, melatonin (endogenous melatonergic agonist), or S32006 (5-HT2C antagonist), and then subjected to acute footshock-stress.


Only chronic agomelatine, but not melatonin or S32006, completely prevented the stress-induced increase of glutamate release in the rat prefrontal/frontal cortex.


These results suggest a potential synergy between melatonergic and serotonergic pathways in the action of agomelatine.