Imipramine treatment up-regulates the expression and function of mGlu2/3 metabotropic glutamate receptors in the rat hippocampus

Matrisciano, F., Storto, M., Ngomba, Richard T. , Cappuccio, I., Caricasole, A., Scaccianoce, S., Riozzi, B., Melchiorri, D. and Nicoletti, F. (2002) Imipramine treatment up-regulates the expression and function of mGlu2/3 metabotropic glutamate receptors in the rat hippocampus. Neuropharmacology, 42 (8). pp. 1008-1015. ISSN 0028-3908

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We examined the effect of a chronic imipramine treatment (10 mg/kg, i.p., once daily for 21 days) on the expression and function of metabotropic glutamate (mGlu) receptors in discrete regions of the rat brain. Chronic imipiramine treatment up-regulated the expression of mGlu2/3 receptor proteins in the hippocampus, nucleus accumbens, cerebral cortex and corpus striatum. Expression of mGlu1a receptor protein was increased exclusively in the hippocampus, whereas no changes in the expression of mGlu4 and mGlu5 receptors or Homer-1a protein were detected. Using hippocampal slices, we examined the stimulation of polyphosphoinositide (PI) hydrolysis induced by mGlu receptor agonists in control and imipramine-treated rats. Imipramine treatment amplified the PI response to the non subtype-selective mGlu receptor agonist, 1S,3R-aminocyclopentane-1,3-dicarboxylated (1S,3R-ACPD) in both hippocampal and cortical slices, but failed to affect the response to the selective mGlu1/5 receptor agonist, S-3,5-dihydroxyphenylglycine (DHPG). Amplification was restored when DHPG was combined with the selective mGlu2/3 receptor agonist, LY379268. In addition, 1S,3R-ACPD-stimulated PI hydrolysis was no longer enhanced in imipramine-treated rats when the mGlu2/3 component of the PI response was abrogated by the antagonist, LY341495. In contrast, the ability of LY379268 to inhibit forskolin-stimulated cAMP formation was reduced in hippocampal slices of rats chronically treated with imipramine. Taken together, these results suggest that neuroadaptive changes in the expression and function of mGlu2/3 receptors occur in response to chronic antidepressants.

Keywords:1 amino 1,3 cyclopentanedicarboxylic acid, 2 amino 2 (2 carboxycyclopropyl) 3 (xanthen 9 yl)propionic acid, 2 amino 4 phosphonobutyric acid, 4 amino 2 oxabicyclo3.1.0hexane 4,6 dicarboxylic acid, brain protein, cyclic AMP, dihydroxyphenylglycine, forskolin, glycine derivative, imipramine, messenger RNA, metabotropic receptor, polyphosphoinositide, protein Homer 1a, unclassified drug, animal tissue, article, brain cortex, brain slice, concentration response, controlled study, corpus striatum, drug effect, hippocampus, hydrolysis, male, nonhuman, nucleus accumbens, priority journal, protein analysis, protein expression, rat, Adrenergic Uptake Inhibitors, Animals, Rats, Rats, Sprague-Dawley, Receptors, Metabotropic Glutamate, Up-Regulation
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:22170
Deposited On:24 Feb 2016 14:44

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