Throughout the central nervous system, many glutamatergic synapses are depressed by the presynaptic action of metabotropic glutamate receptors (mGluRs). Transcriptional alterations of these receptors have been implication in a number of neurological diseases such as temporal lobe epilepsy. The current hypothesis is that downregulation of mGluRs (mainly of group I and III) may facilitate glutamate release in the chronically epileptic hippocampus. Here, we asked the question whether group II mGluRs which mediate the depression of medial perforant path-evoked synaptic responses in dentate granule cells are also downregulated in epileptic tissue. To this end, we tested the effect of the specific group II mGluR agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclo-propyl)glycine (DCG-IV, 10 mM) on excitatory postsynaptic field potentials (fEPSPs) in the middle molecular layer. In control slices, this compound significantly depressed synaptic transmission, but significantly more so in tissue taken from pilocarpine-treated chronically epileptic rats. This depression was accompanied by a significant increase of the paired-pulse ratio in both animal groups indicating a presynaptic mechanism. Moreover, we also used animals that received pilocarpine, but did not develop status epilepticus. In this tissue, the synaptic depression by DCG-IV was not different from control values. To identify the underlying mechanism of this enhanced DCG-IV effect, we performed real-time reverse-transcriptase PCR for both subunits of group II mGluRs (mGluR2 and mGluR3). The quantitative PCR revealed that the presynaptic structure of the medial perforant path, the entorhinal cortex, showed a significant increase of mGluR2-mRNA, but not of mGluR3 transcripts. Immunohistochemistry confirmed the increased expression of group II mGluRs in the epileptic medial molecular layer. These results demonstrate that chronic epilepsy not only may lead to downregulation of mGluRs in the hippocampus, but may also cause enhanced expression of these receptors - at least in the medial perforant path.