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

F. Matrisciano, S. Scaccianoce, P. Del Bianco, I. Panaccione, A. M. Canudas, G. Battaglia, B. Riozzi, R. T. Ngomba, G. Molinaro, R. Tatarelli, D. Melchiorri, Ferdinando Nicoletti

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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.

Original languageEnglish (US)
Pages (from-to)1345-1352
Number of pages8
JournalJournal of Neurochemistry
Volume93
Issue number5
DOIs
Publication statusPublished - Jun 1 2005

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Keywords

  • β-adrenergic receptors
  • Imipramine treatment
  • LY341495
  • LY379268
  • mGlu2/3 receptors
  • Neuroadaptation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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