title: Chronic treatment with agomelatine or venlafaxine reduces depolarization-evoked glutamate release from hippocampal synaptosomes.
abstract: 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.
authors.affiliation: Department of Pharmacy, Unit of Pharmacology and Toxicology and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Milanese
authors.forename: Daniela
authors.initials: D
authors.lastname: Tardito
authors.forename: Laura
authors.initials: L
authors.lastname: Musazzi
authors.forename: Giulia
authors.initials: G
authors.lastname: Treccani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallei
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bonifacino
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gabriel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mocaer
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
authors.forename: Giambattista
authors.initials: G
authors.lastname: Bonanno
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D061207:Calcium Ionophores / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050600:SNARE Proteins / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects*; D050827:Syntaxin 1 / Q000378:metabolism; D000069470:Venlafaxine Hydrochloride; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D061207:Calcium Ionophores; D003511:Cyclohexanols; D018698:Glutamic Acid; D015759:Ionomycin; D011189:Potassium Chloride; D050600:SNARE Proteins; D050827:Syntaxin 1; D000069470:Venlafaxine Hydrochloride; D005680:gamma-Aminobutyric Acid; C084711:agomelatine; D009281:Naphthalenes
references.citation: Cell. 1999 Apr 16;97(2):165-74
references.pmid: 10219238
references.citation: Brain Res. 1986 Apr 30;372(1):115-29
references.pmid: 3011205
references.citation: Drugs. 2012 Jul 9;72(10):1313-33
references.pmid: 22731961
references.citation: BMC Neurosci. 2010 Jun 03;11:68
references.pmid: 20525261
references.citation: Cold Spring Harb Perspect Biol. 2012 Jan 01;4(1):a011353
references.pmid: 22068972
references.citation: Nat Rev Neurosci. 2011 Nov 30;13(1):22-37
references.pmid: 22127301
references.citation: Neuropharmacology. 2012 Jan;62(1):63-77
references.pmid: 21827775
references.citation: Am J Psychiatry. 2010 Nov;167(11):1305-20
references.pmid: 20843874
references.citation: Brain Res. 2012 Jul 23;1466:91-8
references.pmid: 22647752
references.citation: PLoS One. 2010 Jan 05;5(1):e8566
references.pmid: 20052403
references.citation: J Neurochem. 2006 Feb;96(3):656-68
references.pmid: 16405496
references.citation: World J Biol Psychiatry. 2011 Dec;12(8):574-87
references.pmid: 21999473
references.citation: J Neurosci. 2005 Mar 30;25(13):3270-9
references.pmid: 15800181
references.citation: Neuron. 2007 Oct 25;56(2):226-38
references.pmid: 17964242
references.citation: Nat Rev Drug Discov. 2007 Mar;6(3):189-201
references.pmid: 17330070
references.citation: Biol Psychiatry. 2013 Jun 15;73(12):1180-8
references.pmid: 23273725
references.citation: J Pharmacol Exp Ther. 2003 Sep;306(3):954-64
references.pmid: 12750432
references.citation: Pharmacol Ther. 2001 Feb;89(2):149-70
references.pmid: 11316518
references.citation: Annu Rev Neurosci. 2004;27:509-47
references.pmid: 15217342
references.citation: Neuropsychopharmacology. 2007 Dec;32(12):2511-9
references.pmid: 17356571
references.citation: Trends Cogn Sci. 2012 Jan;16(1):61-71
references.pmid: 22197477
references.citation: Eur J Neurosci. 2007 May;25(10):3109-14
references.pmid: 17561824
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2003 Jun;367(6):553-61
references.pmid: 12764576
references.citation: Nature. 2012 Oct 11;490(7419):201-7
references.pmid: 23060190
references.citation: Pharmacol Biochem Behav. 2012 Feb;100(4):656-64
references.pmid: 21889952
references.citation: Prog Neurobiol. 2002 Nov;68(4):287-309
references.pmid: 12498989
references.citation: Pharmacol Biochem Behav. 2012 Feb;100(4):688-704
references.pmid: 21536063
references.citation: Nat Neurosci. 2001 Apr;4(4):391-5
references.pmid: 11276229
references.citation: Nat Rev Drug Discov. 2010 Aug;9(8):628-42
references.pmid: 20577266
references.citation: Trends Neurosci. 2012 Jan;35(1):47-56
references.pmid: 22217452