title: The effects of antidepressant treatment in prenatally stressed rats support the glutamatergic hypothesis of stress-related disorders.
abstract: Abnormalities of synaptic transmission in the hippocampus represent an integral part of the altered programming triggered by early life stress, which enhances the vulnerability to stress-related disorders in the adult life. Rats exposed to prenatal restraint stress (PRS) develop enduring biochemical and behavioral changes characteristic of an anxious/depressive-like phenotype. Most neurochemical abnormalities in PRS rats are found in the ventral hippocampus, a region that encodes memories related to stress and emotions. We have recently demonstrated a causal link between the reduction of glutamate release in the ventral hippocampus and anxiety-like behavior in PRS rats. To confer pharmacological validity to the glutamatergic hypothesis of stress-related disorders, we examined whether chronic treatment with two antidepressants with different mechanisms of action could correct the defect in glutamate release and associated behavioral abnormalities in PRS rats. Adult unstressed or PRS rats were treated daily with either agomelatine (40 mg/kg, i.p.) or fluoxetine (5 mg/kg, i.p.) for 21 d. Both treatments reversed the reduction in depolarization-evoked glutamate release and in the expression of synaptic vesicle-associated proteins in the ventral hippocampus of PRS rats. Antidepressant treatment also corrected abnormalities in anxiety-/depression-like behavior and social memory performance in PRS rats. The effect on glutamate release was strongly correlated with the improvement of anxiety-like behavior and social memory. These data offer the pharmacological demonstration that glutamatergic hypofunction in the ventral hippocampus lies at the core of the pathological phenotype caused by early life stress and represents an attractive pharmacological target for novel therapeutic strategies.
authors: Istituto di Ricovero e Cura a Carattere Scientifico, Centro Neurolesi "Bonino-Pulejo," Messina 98124, Italy, Neural Plasticity Team-Unité Mixte de Recherche 8576 Centre National de la Recherche Scientifique/Université Lille 1, Department of Structural and Functional Glycobiology, F-59655 Villeneuve d'Ascq, France, Institutes de Recherches Internationales Servier, 92150 Suresnes, France, Department of Pharmacy, University of Genoa, Genoa 16146, Italy, Sapienza University of Rome and Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, Pozzilli 86077, Italy, and International Associated Laboratory-Prenatal Stress and Neurodegenerative Diseases, F-59655 Villeneuve d'Ascq, IT-00185 Rome, IT-86077 Pozzilli.
authors: Jordan
authors: J
authors: Marrocco
authors: Marie-Line
authors: ML
authors: Reynaert
authors: Eleonora
authors: E
authors: Gatta
authors: Cecilia
authors: C
authors: Gabriel
authors: Elisabeth
authors: E
authors: Mocaër
authors: Silvia
authors: S
authors: Di Prisco
authors: Elisa
authors: E
authors: Merega
authors: Anna
authors: A
authors: Pittaluga
authors: Ferdinando
authors: F
authors: Nicoletti
authors: Stefania
authors: S
authors: Maccari
authors: Sara
authors: S
authors: Morley-Fletcher
authors: Jérôme
authors: J
authors: Mairesse
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D018698:Glutamic Acid