The effects of antidepressant treatment in prenatally stressed rats support the glutamatergic hypothesis of stress-related disorders

Jordan Marrocco, Marie Line Reynaert, Eleonora Gatta, Cecilia Gabriel, Elisabeth Mocaër, Silvia Di Prisco, Elisa Merega, Anna Pittaluga, Ferdinando Nicoletti, Stefania Maccari, Sara Morley-Fletcher, Jérôme Mairesse

Research output: Contribution to journalArticlepeer-review

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.Wehave 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.

Original languageEnglish
Pages (from-to)2015-2024
Number of pages10
JournalJournal of Neuroscience
Volume34
Issue number6
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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