Chronic treatment with agomelatine or venlafaxine reduces depolarization-evoked glutamate release from hippocampal synaptosomes

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


  • Marco Milanese, Department of Pharmacy, Unit of Pharmacology and Toxicology and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy.
  • ,
  • Daniela Tardito
  • ,
  • Laura Musazzi
  • ,
  • Giulia Treccani
  • Alessandra Mallei
  • ,
  • Tiziana Bonifacino
  • ,
  • Cecilia Gabriel
  • ,
  • Elisabeth Mocaer
  • ,
  • Giorgio Racagni
  • ,
  • Maurizio Popoli
  • ,
  • Giambattista Bonanno

BACKGROUND: Growing compelling evidence from clinical and preclinical studies has demonstrated the primary role of alterations of glutamatergic transmission in cortical and limbic areas in the pathophysiology of mood disorders. Chronic antidepressants have been shown to dampen endogenous glutamate release from rat hippocampal synaptic terminals and to prevent the marked increase of glutamate overflow induced by acute behavioral stress in frontal/prefrontal cortex. Agomelatine, a new antidepressant endowed with MT1/MT2 agonist and 5-HT2C serotonergic antagonist properties, has shown efficacy at both preclinical and clinical levels.

RESULTS: Chronic treatment with agomelatine, or with the reference drug venlafaxine, induced a marked decrease of depolarization-evoked endogenous glutamate release from purified hippocampal synaptic terminals in superfusion. No changes were observed in GABA release. This effect was accompanied by reduced accumulation of SNARE protein complexes, the key molecular effector of vesicle docking, priming and fusion at presynaptic membranes.

CONCLUSIONS: Our data suggest that the novel antidepressant agomelatine share with other classes of antidepressants the ability to modulate glutamatergic transmission in hippocampus. Its action seems to be mediated by molecular mechanisms located on the presynaptic membrane and related with the size of the vesicle pool ready for release.

Original languageEnglish
JournalB M C Neuroscience
Pages (from-to)75
Publication statusPublished - 2013

    Research areas

  • Acetamides, Analysis of Variance, Animals, Antidepressive Agents, Calcium Ionophores, Cyclohexanols, Glutamic Acid, Hippocampus, Ionomycin, Male, Potassium Chloride, Rats, Rats, Sprague-Dawley, SNARE Proteins, Synaptosomes, Syntaxin 1, Venlafaxine Hydrochloride, gamma-Aminobutyric Acid, Journal Article, Research Support, Non-U.S. Gov't

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ID: 103338940