POTENTIATION OF SYNAPTIC TRANSMISSION IN THE RAT DENTATE GYRUS IN-VITRO BY (S)-3,5-DIHYDROXYPHENYLGLYCINE ((S)-DHPG)

The direct activation of metabotropic glutamate receptors (mGluRs) by 1S,3R-aminocyclopentane dicarboxylate (1S,3R-ACPD), has previously bee n shown to induce a relatively fast (maximum at 10 min) and slow (90 m in) onset long-term potentiation (LTP) of synaptic transmission in the hippocampus. Here we report the first evidence for a relatively fast onset LTP of synaptic transmission in the immature male rat (50-100 g) dentate gyrus in vitro by application of the mGluR type I agonist, (S )-3,5-dihydroxyphenylglycine ((S)-DHPG; 20 mu M). Bath application of (S)-DHPG caused a transient depression of the field excitatory postsyn aptic potential (EPSP) slope, followed after washout by a relatively r apidly developing potentiation of synaptic transmission to a maximum i ncrease at 12-15 min (161.1 +/- 11.4% compared to controls at 15 min; n = 8). This effect was not observed following perfusion with the enan tiomer (R,S)-DHPG at the same dose. The (S)-DHPG potentiation occluded tetanically induced LTP and vice versa. The potentiation was antagoni sed by the non-specific mGluR antagonist (R,S)-alpha-methyl-4-carboxyp henylglycine ((R,S)-MCPG) at high doses (500-1000 mu M) but was unaffe cted in the presence of the N-methyl-D-aspartate (NMDA) receptor block er, D(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 50 mu M) Our result s demonstrate a robust NMDA-independent LTP induced by (S)-DHPG that o ccludes tetanically induced LTP. (C) 1997 Elsevier Science Ireland Ltd .