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.