It has been suggested that the induction of long-term depression (LTD) may be developmentally regulated since LTD can be readily induced by LFS in slices from young but not adult animals. However, we have recently reported that paired pulse low frequency stimulation (PP-LFS) can reliably induce LTD in the CA1 region of adult hippocampal slices. We now describe the role of glutamate receptors in the induction of LTD in adult hippocampus. The induction of LTD was prevented by the combined application of AMPA/kainate and metabotropic glutamate (mGlu) receptor antagonists (CNQX and LY341495). However, LTD was not blocked by the co-application of NMDA and mGlu receptor antagonists nor by the co-application of NMDA and AMPA/kainate receptor antagonists. Taken together, the above results suggest that activation of either AMPA/kainate or mGlu receptors is sufficient to induce LTD. Therefore, these results suggest that PP-LFS can efficiently activate AMPA/kainate and mGlu receptors in order to induce long-lasting synaptic depression in the CA1 region of the adult hippocampus in vitro.