TY - JOUR
T1 - Metabotropic glutamate receptors and neuroadaptation to antidepressants
T2 - Imipramine-induced down-regulation of β-adrenergic receptors in mice treated with metabotropic glutamate 2/3 receptor ligands
AU - Matrisciano, F.
AU - Scaccianoce, S.
AU - Del Bianco, P.
AU - Panaccione, I.
AU - Canudas, A. M.
AU - Battaglia, G.
AU - Riozzi, B.
AU - Ngomba, R. T.
AU - Molinaro, G.
AU - Tatarelli, R.
AU - Melchiorri, D.
AU - Nicoletti, Ferdinando
PY - 2005/6
Y1 - 2005/6
N2 - 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.
AB - 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.
KW - Imipramine treatment
KW - LY341495
KW - LY379268
KW - Neuroadaptation
KW - mGlu2/3 receptors
KW - β-adrenergic receptors
UR - http://www.scopus.com/inward/record.url?scp=20144385463&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144385463&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2005.03141.x
DO - 10.1111/j.1471-4159.2005.03141.x
M3 - Article
C2 - 15934953
AN - SCOPUS:20144385463
SN - 0022-3042
VL - 93
SP - 1345
EP - 1352
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 5
ER -