title: Anxiety-like behavior of prenatally stressed rats is associated with a selective reduction of glutamate release in the ventral hippocampus.
abstract: Abnormalities of synaptic transmission and plasticity in the hippocampus represent an integral part of the altered programming triggered by early life stress. Prenatally restraint stressed (PRS) rats develop long-lasting biochemical and behavioral changes, which are the expression of an anxious/depressive-like phenotype. We report here that PRS rats showed a selective impairment of depolarization- or kainate-stimulated glutamate and [(3)H]d-aspartate release in the ventral hippocampus, a region encoding memories related to stress and emotions. GABA release was unaffected in PRS rats. As a consequence of reduced glutamate release, PRS rats were also highly resistant to kainate-induced seizures. Abnormalities of glutamate release were associated with large reductions in the levels of synaptic vesicle-related proteins, such as VAMP (synaptobrevin), syntaxin-1, synaptophysin, synapsin Ia/b and IIa, munc-18, and Rab3A in the ventral hippocampus of PRS rats. Anxiety-like behavior in male PRS (and control) rats was inversely related to the extent of depolarization-evoked glutamate release in the ventral hippocampus. A causal relationship between anxiety-like behavior and reduction in glutamate release was demonstrated using a mixture of the mGlu2/3 receptor antagonist, LY341495, and the GABA(B) receptor antagonist, CGP52432, which was shown to amplify depolarization-evoked [(3)H]d-aspartate release in the ventral hippocampus. Bilateral microinfusion of CGP52432 plus LY341495 in the ventral hippocampus abolished anxiety-like behavior in PRS rats. These findings indicate that an impairment of glutamate release in the ventral hippocampus is a key component of the neuroplastic program induced by PRS, and that strategies aimed at enhancing glutamate release in the ventral hippocampus correct the "anxious phenotype" caused by early life stress.
authors.affiliation: Neural Plasticity Team-UMR CNRS/USTL 8576 Structural and Functional Glycobiology Unit, North University of Lille, 59655 Villeneuve d'Ascq France, IRCCS Neuromed, 86077 Pozzilli, Italy.
authors.forename: Jordan
authors.initials: J
authors.lastname: Marrocco
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mairesse
authors.forename: Richard Teke
authors.initials: RT
authors.lastname: Ngomba
authors.forename: Viviana
authors.initials: V
authors.lastname: Silletti
authors.forename: Gilles
authors.initials: G
authors.lastname: Van Camp
authors.forename: Hammou
authors.initials: H
authors.lastname: Bouwalerh
authors.forename: Maria
authors.initials: M
authors.lastname: Summa
authors.forename: Anna
authors.initials: A
authors.lastname: Pittaluga
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Stefania
authors.initials: S
authors.lastname: Maccari
authors.forename: Sara
authors.initials: S
authors.lastname: Morley-Fletcher
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D001596:Benzylamines / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007608:Kainic Acid; D008297:Male; D051938:Munc18 Proteins / Q000378:metabolism; D010721:Phosphinic Acids / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D050827:Syntaxin 1 / Q000378:metabolism; D014966:Xanthenes / Q000494:pharmacology; D020826:rab3A GTP-Binding Protein / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001596:Benzylamines; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; C114624:LY 341495; D051938:Munc18 Proteins; D010721:Phosphinic Acids; D050683:R-SNARE Proteins; D016704:Synapsins; D016708:Synaptophysin; D050827:Syntaxin 1; D014966:Xanthenes; C083008:CGP 52432; D018698:Glutamic Acid; D020826:rab3A GTP-Binding Protein; D007608:Kainic Acid