title: Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats.
abstract: OBJECTIVE
  The rat model of prenatal restraint stress (PRS) replicates factors that are implicated in the etiology of anxious/depressive disorders. We used this model to test the therapeutic efficacy of agomelatine, a novel antidepressant that behaves as a mixed MT1/MT2 melatonin receptor agonist/5-HT(2c) serotonin receptor antagonist.
  
  
  RESULTS
  Adult PRS rats showed behavioral, cellular, and biochemical abnormalities that were consistent with an anxious/depressive phenotype. These included an increased immobility in the forced swim test, an anxiety-like behavior in the elevated plus maze, reduced hippocampal levels of phosphorylated cAMP-responsive element binding protein (p-CREB), reduced hippocampal levels of mGlu2/3 and mGlu5 metabotropic glutamate receptors, and reduced neurogenesis in the ventral hippocampus, the specific portion of the hippocampus that encodes memories related to stress and emotions. All of these changes were reversed by a 3- or 6-week treatment with agomelatine (40-50 mg/kg, i.p., once a day). Remarkably, agomelatine had no effect in age-matched control rats, thereby behaving as a "disease-dependent" drug.
  
  
  CONCLUSIONS
  These data indicate that agomelatine did not act on individual symptoms but corrected all aspects of the pathological epigenetic programming triggered by PRS. Our findings strongly support the antidepressant activity of agomelatine and suggest that the drug impacts mechanisms that lie at the core of anxious/depressive disorders.
authors.affiliation: Neuroplasticity Team, UMR 8576 CNRS Structural and Functional Glycobiology Unit, University Lille North of France (USTL), 59655, Villeneuve d'Ascq, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Morley-Fletcher
authors.forename: Jerome
authors.initials: J
authors.lastname: Mairesse
authors.forename: Amelie
authors.initials: A
authors.lastname: Soumier
authors.forename: Mounira
authors.initials: M
authors.lastname: Banasr
authors.forename: Francesca
authors.initials: F
authors.lastname: Fagioli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gabriel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mocaer
authors.forename: Annie
authors.initials: A
authors.lastname: Daszuta
authors.forename: Bruce
authors.initials: B
authors.lastname: McEwen
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Stefania
authors.initials: S
authors.lastname: Maccari
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001007:Anxiety / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001522:Behavior, Animal / Q000187:drug effects*; D050882:CREB-Binding Protein / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003627:Data Interpretation, Statistical; D003863:Depression / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications*; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D050882:CREB-Binding Protein; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C084711:agomelatine; D009281:Naphthalenes; C494365:Crebbp protein, rat