Metabotropic glutamate receptors and neuroadaptation to antidepressants: imipramine-induced down-regulation of β-adrenergic receptors in mice treated with metabotropic glutamate 2/3 receptor ligands

Matrisciano, F. and Scaccianoce, S. and Del Bianco, P. and Panaccione, I. and Canudas, A. M. and Battaglia, G. and Riozzi, B. and Ngomba, R. T. and Molinaro, G. and Tatarelli, R. and Melchiorri, D. and Nicoletti, F. (2005) Metabotropic glutamate receptors and neuroadaptation to antidepressants: imipramine-induced down-regulation of β-adrenergic receptors in mice treated with metabotropic glutamate 2/3 receptor ligands. Journal of Neurochemistry, 93 (5). pp. 1345-1352. ISSN 0022-3042

Full content URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-...

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Item Type:Article
Item Status:Live Archive

Abstract

Antidepressant drugs have a clinical latency that correlates with the development of neuroadaptive changes, including down-regulation of β-adrenergic receptors in different brain regions. The identification of drugs that shorten this latency will have a great impact on the treatment of major depressive disorders. We report that the time required for the antidepressant imipramine to reduce the expression of β-adrenergic receptors in the hippocampus is reduced by a co-administration with centrally active ligands of type 2/3 metabotropic glutamate (mGlu2/3) receptors. Daily treatment of mice with imipramine alone (10 mg/kg, i.p.) reduced the expression of β-adrenergic receptors in the hippocampus after 21 days, but not at shorter times, as assessed by western blot analysis of β1-adrenergic receptors and by the amount of specifically bound [3H]CGP-12177, a selective β-adrenergic receptor ligand. Down-regulation of β-adrenergic receptors occurred at shorter times (i.e. after 14 days) when imipramine was combined with low doses (0.5 mg/kg, i.p.) of the selective mGlu2/3 receptor agonist LY379268, or with the preferential mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.). Higher doses of LY379268 (2 mg/kg, i.p.) were inactive. This intriguing finding suggests that neuroadaptation to imipramine – at least as assessed by changes in the expression of β1-adrenergic receptors – is influenced by drugs that interact with mGlu2/3 receptors and stimulates further research aimed at establishing whether any of these drugs can shorten the clinical latency of classical antidepressants

Keywords:2 amino 2 (2 carboxycyclopropyl) 3 (xanthen 9 yl)propionic acid, 4 (3 tert butylamino 2 hydroxypropoxy) 2 benzimidazolone, 4 amino 2 oxabicyclo3.1.0hexane 4,6 dicarboxylic acid, antidepressant agent, beta adrenergic receptor, desipramine, forskolin, imipramine, ligand, metabotropic receptor, metabotropic receptor 2, metabotropic receptor 3, adaptation, animal cell, animal tissue, article, brain region, chemical binding, controlled study, down regulation, hippocampus, latent period, major depression, medical research, mouse, nonhuman, priority journal, protein interaction, receptor binding, Adaptation, Physiological, Amino Acids, Animals, Antidepressive Agents, Tricyclic, Bicyclo Compounds, Heterocyclic, Down-Regulation, Excitatory Amino Acid Antagonists, Ligands, Male, Mice, Mice, Inbred Strains, Nervous System Physiology, Reaction Time, Receptors, Adrenergic, beta, Receptors, Metabotropic Glutamate, 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:22164
Deposited On:18 Feb 2016 18:32

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