Hippocampal long-term depression (LTD) involves a long-lasting decrease in synaptic transmission which is induced by low-frequency stimulation (LFS). Evidence exists that variability in the responsiveness of rat strains to LFS occurs. Thus, Wistar rats readily express LTD in vivo, whereas Hooded Lister rats demonstrate at best short-term depression (STD) in response to LFS. Group III metabotropic glutamate receptor (mGluR)-involvement in the induction of LTD in freely moving rats has not yet been investigated. This study therefore examined the effect of group III mGluR activation and inhibition on LTD expression, and evaluated these effects in Wistar and Hooded Lister rats. Animals were chronically implanted with recording and bipolar stimulating electrodes in the CA1 region, and an injection cannula in the lateral cerebral ventricle. LFS (1 Hz, 900 pulses) induced LTD in Wistar, and STD in Hooded Lister rats. Agonist priming with L-2-amino-4-phosphonobutanoic acid (AP4, 400 nmol/5 microl) facilitated LTD expression in Hooded Lister but not Wistar rats. The antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine inhibited the facilitatory effects of AP4 in Hooded Lister- and impaired LTD expression in Wistar rats. These data imply a role for group III mGluRs in hippocampal LTD in vivo, and suggest that differences in this mGluR system may account, in part, for strain-dependent variations in LTD expression.