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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
Author(s) -
Matrisciano F.,
Scaccianoce S.,
Del Bianco P.,
Panaccione I.,
Canudas A. M.,
Battaglia G.,
Riozzi B.,
Ngomba R. T.,
Molinaro G.,
Tatarelli R.,
Melchiorri D.,
Nicoletti F.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03141.x
Subject(s) - metabotropic receptor , metabotropic glutamate receptor , receptor , pharmacology , imipramine , agonist , medicine , endocrinology , adrenergic receptor , glutamate receptor , chemistry , metabotropic glutamate receptor 5 , long term depression , ampa receptor , alternative medicine , pathology
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 β 1 ‐adrenergic receptors and by the amount of specifically bound [ 3 H]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 β 1 ‐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.