On the role of metabotropic glutamate receptors in the mechanisms of action of antidepressants.
Effects of repeated imipramine treatment on inositol phosphates accumulation and on the reactivity of neurons to metabotropic glutamate receptor (mGlu) agonist (1S,3R)-1-carboxycyclopentane-3acetic acid (1S,3R-ACPD) were investigated in the rat hippocampal slices. The concentration-dependent increase in inositol phosphate accumulation in the slices from CA1 region of hippocampus induced by 1S,3R-ACPD was not modified by imipramine treatment. 1S,3R-ACPD produced a concentration-dependent increase in population spike amplitude recorded in the CA1 cell layer. This effect of 1S,3R-ACPD was markedly attenuated by repeated imipramine administration. Our results indicate that antidepressant treatment may induce a subsensitivity of mGlu receptors in the CA1 region of hippocampus when estimated by electrophysiological, but not biochemical measures.