Anxiety-like behavior of prenatally stressed rats is associated with a selective reduction of glutamate release in the ventral hippocampus

Marrocco, J., Mairesse, J., Ngomba, R.T. , Silletti, V., Van Camp, G., Bouwalerh, H., Summa, M., Pittaluga, A., Nicoletti, F., Maccari, S. and Morley-Fletcher, S. (2012) Anxiety-like behavior of prenatally stressed rats is associated with a selective reduction of glutamate release in the ventral hippocampus. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 32 (48). pp. 17143-17154. ISSN 0270-6474

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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 3HD-aspartate release in the ventral hippo campus, a region encoding memories related to stress and emotions. GABA release was un affected 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 usingamixtureofthemGlu2/3 receptor antagonist, LY341495, and the GABAB receptor antagonist, CGP52432, which was shown to amplify depolarization-evoked 3HD-aspartate release in the ventral hippocampus. Bilateral micro infusion 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 neuro plastic 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.

Keywords:2 amino 2 (2 carboxycyclopropyl) 3 (xanthen 9 yl) propionic acid, 2 amino 2 (2 carboxycyclopropyl) 3 (xanthen 9 yl)propionic acid, 4 aminobutyric acid, 3 (3, 4 dichlorobenzylamino) propyl (diethoxymethyl) phosphinic acid, 3 (3,4 dichlorobenzylamino)propyl(diethoxymethyl)phosphinic acid, dextro aspartic acid, excitatory amino acid transporter, excitatory amino acid transporter 1, glutamic acid, Munc18 protein, Rab protein, synapsin I, synapsin II, synaptobrevin, synaptophysin, synaptosomal associated protein 25, syntaxin 1, unclassified drug, vesicular glutamate transporter 1, animal experiment, animal model, animal tissue, anxiety, article, behavior, controlled study, depolarization, electroencephalography, electromyography, female, high performance liquid chromatography, hippocampus, male, maze test, neurotransmitter release, nonhuman, prenatal stress, priority journal, protein expression, rat, seizure, spike wave, synapse vesicle, synaptosome, Western blotting, Amino Acids, Animals, Behavior, Animal, Benzylamines, Excitatory Amino Acid Antagonists, GABA-A Receptor Antagonists, Kainic Acid, Munc18 Proteins, Phosphinic Acids, Pregnancy, Prenatal Exposure Delayed Effects, R-SNARE Proteins, rab3A GTP-Binding Protein, Rats, Rats, Sprague-Dawley, Seizures, Stress, Psychological, Synapsins, Synaptic Transmission, Xanthenes
Subjects:B Subjects allied to Medicine > B210 Pharmacology
B Subjects allied to Medicine > B140 Neuroscience
Divisions:College of Science > School of Pharmacy
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ID Code:22147
Deposited On:04 Feb 2016 17:49

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