It has been demonstrated by others in vitro that application of 1S,3R-aminocyclopentane-2,3-dicarboxylic acid (ACPD) facilitates long-term potentiation and triggers a slow-onset potentiation in the hippocampus. This study examined the effect of ACPD in the dentate gyrus when applied in vivo. Weak tetanisation produced a short-term potentiation of field excitatory post-synaptic potential (EPSP) and population spike. A similar response was seen upon application of ACPD (40 microM in 5 microl vehicle) via the lateral cerebral ventricle 30 min prior to tetanus, whereas ACPD (80 microM/5 microl) facilitated short-term potentiation into long-term potentiation. (R,S)-alpha-Methyl-4-carboxyphenyl-glycine (MCPG 200 mM/5 microl), completely inhibited this effect. ACPD had no effect on baseline recordings at 40 and 80 microM/5 miccrol, however 4 mM/5 microl ACPD induced a slow-onset potentiation of field EPSP and population spike which was maintained for over 4 h. MCPG or D-2-amino-5-phosphonopentanoate (AP5 20 mM/5 microl) applied prior to ACPD completely inhibited this effect. These results suggest that previously reported in vitro effects of ACPD in the CA1 region, also occur in the dentate gyrus in vivo. Furthermore, they confirm that activation of mGlu receptors by ACPD in vivo facilitates long-term potentiation, and indicate that in the dentate gyrus, ACPD-induced slow-onset potentiation is NMDA receptor-dependent.