Metabotropic glutamate group II receptors are responsible for the depression of synaptic transmission induced by ACPD in the dentate gyrus

The functional role of metabotropic glutamate (mGlu) receptors in the rat dentate gyrus was investigated. By using extracellular recording techniques in slices, it was found that the depression induced by the mGlu receptor agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylate (ACPD) was mediated through the mGlu group II receptors. The mGlu receptor antagonist cu-methyl-4-carboxyphenylglycine (MCPG) (500 mu M), active at group I and group II subtype receptors, was effective in antagonizing the ACPD (30 mu M)-induced depression of the excitatory field potentials. An antagonist selective for group I, (S)-4-carboxyphenylglycine (4CPG), did not block the effects induced by ACPD, but by itself produced a dose-dependent depression of the field potentials. This ACPD-like effect shown at high concentrations of 4CPG (300 mu M) is explained by its group II receptor agonistic properties and was blocked by bath application of MCPG (500 mu M). A selective agonist of group I, (S)-3-hydroxyphenylglycine (3-HPG), did not cause any depression of synaptic transmission. However, the selective mGlu group II receptor agonist, (2S,3S,4S)-alpha-(carboxycyclopropyl)glycin (L-CCG-I), induced a marked dose-dependent depression and its action was blocked by MCPG (500 mu M). Furthermore, the selective mGlu group III receptor antagonist, alpha-methyl-L-2-amino-4-phosphonobutyrate (MAP4) (500 mu M), was not able to antagonize the depression induced by ACPD (30 mu M), but was effective in blocking the action induced by the selective mGlu group III agonist, L-2-amino-4-phosphonobutyrate (L-AP4) (100 mu M). These results indicate that mGlu group II receptors, but not groups I or III, are involved in the depression of synaptic transmission in the dentate area of the hippocampus induced by ACPD.