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

BMC Neuroscience

Giambattista Bonanno²  Maurizio Popoli³  Giorgio Racagni⁴  Elisabeth Mocaer¹  Cecilia Gabriel¹  Tiziana Bonifacino²  Alessandra Mallei³  Giulia Treccani³  Laura Musazzi³  Daniela Tardito³  Marco Milanese² 

[1] Institut de Recherches Internationales Servier (I.R.I.S.), Suresnes, France;Department of Pharmacy, Unit of Pharmacology and Toxicology and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy;Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases (CEND), Università degli Studi di Milano, Via Balzaretti, Milano, 9-20133, Italy;Istituto di Ricovero e Cura a Carattere Scientifico San Giovanni di Dio - Fatebenefratelli, Brescia, Italy

关键词: Hippocampus;    Synaptosomes;    Glutamate;    Venlafaxine;    Agomelatine;    Antidepressant;   

Others  :  1140211
DOI  :  10.1186/1471-2202-14-75

 received in 2013-04-09, accepted in 2013-07-26,  发布年份 2013

【 摘 要 】

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-HT_2C 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.

【 授权许可】

   
2013 Milanese et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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