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.
BACKGROUND
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.


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


CONCLUSIONS
These results suggest a potential synergy between melatonergic and serotonergic pathways in the action of agomelatine.
Center of Neuropharmacology - Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Italy.
Daniela
D
Tardito
Marco
M
Milanese
Tiziana
T
Bonifacino
Laura
L
Musazzi
Massimo
M
Grilli
Alessandra
A
Mallei
Elisabeth
E
Mocaer
Cecilia
C
Gabriel-Gracia
Giorgio
G
Racagni
Maurizio
M
Popoli
Giambattista
G
Bonanno
D000081:Acetamides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004597:Electroshock; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008550:Melatonin / Q000819:agonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D044094:Receptors, Melatonin / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D009281:Naphthalenes
D000081:Acetamides; D002492:Central Nervous System Depressants; D018698:Glutamic Acid; D007211:Indoles; D008550:Melatonin; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; D044094:Receptors, Melatonin; D005680:gamma-Aminobutyric Acid; C533966:S32006; C084711:agomelatine; D009281:Naphthalenes