Reduced activity of hippocampal group-I metabotropic glutamate receptors in learning-prone rats

Cinque, C., Zuena, A .R., Casolini, P. , Ngomba, Richard T., Melchiorri, D., Maccari, S., Nicoletti, F., Di Giorgi Gerevini, V. and Catalani, A. (2003) Reduced activity of hippocampal group-I metabotropic glutamate receptors in learning-prone rats. Neuroscience, 122 (1). pp. 277-284. ISSN 0306-4522

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Following the hypothesis of the “signal-to-noise” ratio (Riedel, 1996) we examined whether changes in the activity of group-I metabotropic glutamate (mGlu) receptors in the hippocampus are associated with a condition that specifically enhances the learning capacity in rats. As a model, we used rats that had been nursed by mothers drinking a solution of corticosterone (13.5 mg of daily intake of corticosterone hemisuccinate) during the lactation period. These rats were prone to learn, as indicated by a better performance in a passive avoidance test. Stimulation of polyphosphoinositide (PI) hydrolysis by the mGlu receptor agonist, 1S,3R-1-amino-cyclopentan-1,3-dicarboxylic acid (1S,3R-ACPD), was attenuated in hippocampal slices prepared from corticosterone-nursed male and female rats at 30 or 60 days of postnatal life, an age at which an increased learning capacity could be demonstrated. This effect was specific because the PI response to carbamylcholine was unchanged. A reduced PI hydrolysis in corticosterone-nursed rats was also observed when group-I mGlu receptors (i.e. mGlu1 and -5 receptors) were selectively activated using 3,5-dihydroxyphenylglycine or 1S,3R-APCD combined with the selective group-II mGlu receptor antagonist, 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)propionate. Western blot analysis showed a selective reduction in the expression of mGlu1a receptor protein in the hippocampus of corticosterone-nursed rats, whereas expression of mGlu5 and mGlu2/3 receptors was unchanged. The reduction in mGlu-receptor mediated PI hydrolysis in the hippocampus may contribute to the greater learning capacity of corticosterone-nursed rats by reducing the background noise over which a specific signal must be superimposed during learning. This hypothesis was supported by the evidence that mGlu-receptor stimulated PI hydrolysis was amplified in hippocampal slices from rats subjected to a passive avoidance learning paradigm, and that this amplification was greater in slices from corticosterone-nursed rats of both sexes.

Keywords:1 amino 1,3 cyclopentanedicarboxylic acid, 2 amino 2 (2 carboxycyclopropyl) 3 (xanthen 9 yl)propionic acid, corticosteroid, messenger RNA, metabotropic receptor, metabotropic receptor agonist, metabotropic receptor antagonist, polyphosphoinositide, animal experiment, animal tissue, article, attenuation, brain slice, controlled study, female, hippocampus, lactation, male, nonhuman, passive avoidance, perinatal period, priority journal, protein expression, protein hydrolysis, rat, receptor intrinsic activity, reduction, signal noise ratio, species comparison, state dependent learning, task performance, Western blotting, Animals, Association Learning, Avoidance Learning, Blotting, Western, Corticosterone, Cycloleucine, Hydrolysis, Phosphatidylinositol Phosphates, Rats, Rats, Wistar, Receptors, Metabotropic Glutamate
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:22167
Deposited On:24 Feb 2016 14:31

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