Developmental regulation of hippocampal excitatory synaptic transmission by metabotropic glutamate receptors

1 The aims of this study were, to use agonists selective for the 3 mGlu receptor groups to identify developmental changes in their effects, and to assess the usefulness of proposed selective antagonists as pharmacological tools. 2 Hippocampal slices (400 mu m) were prepared from neonate (9-14 days) and young adult (5-7 weeks) Sprague-Dawley rats. Field excitatory postsynaptic potentials (fEPSP) were recorded from CAI. 3 DHPG (100 mu M), a group I agonist, produced a slowly developing enhancement of fEPSP slope in slices from adults. In slices from neonates, DHPG (75 mu M) depressed fEPSP slope. 4 DCG-IV (500 nM), a group II agonist, did not affect the fEPSP recorded from slices from adults whereas perfusion in neonate slices produced a sustained depression. 5 The group III agonist L-AP4 (50 mu M) was ineffective in adult slices but depressed fEPSP slope in slices prepared from neonates. 6 DHPG-induced depression of fEPSP slope was inhibited by 4-CPG (400 mu M), a group I antagonist, but was unaffected by MCCG (500 mu M) and MAP4 (500 mu M), group II and III receptor antagonists respectively. MCCG but not MAP4 antagonized the effects of DCG-IV with 4-CPG producing variable effects. The effect of L-AP4 was unaffected by MCCG, blocked by MAP4, and enhanced by 4-CPG. 7 The results show that the effects of the agonists for all groups of mGlu receptors are developmentally regulated. Furthermore, MCCG and MAP4 behave as effective and selective antagonists for group TI and group III mGlu receptors respectively, whereas the usefulness of 4-CPG as a group I antagonist may be limited.