GROUP-II AND GROUP-III METABOTROPIC GLUTAMATE RECEPTORS MODULATE PAIRED-PULSE DEPRESSION IN THE RAT DENTATE GYRUS IN-VITRO

We have investigated the effect of a number of group I, II and III met abotropic glutamate (mGlu) receptor agonists and antagonists on paired pulse depression in the medial perforant path of the rat dentate gyru s in vitro. A triphasic pattern of a large depression at short interva ls (10-50 ms), a reduction of this depression at intermediate interval s (50-200 ms) and again a large depression at late intervals (> 200 ms ) was observed. The group I mGlu receptor agonist, (S)-3,5-dihydroxy p henylglycine ((S)-DHPG; 20 mu M) had no significant effect on paired p ulse depression at any interstimulus intervals. The mGlu receptor grou p II and III agonists, L-CCG-1 ((2S,3S,4S)-alpha-(carboxy-cyclopropyl) -glycine), DCG-IV ((2S,1'R,2'R,3'R)-2-2',3'-dicarboxy cyclopropylglyci ne), 1S,3R-ACPD (1S,3R-1-aminocyclopentate-1,3-dicarboxylic acid) and L-AP4 (L-2-amino-4-phosphono butyric acid) reduced paired pulse depres sion at interstimulus intervals of 200 ms or less. Application of the non specific mGlu receptor antagonist, MCPG (alpha-methyl carboxy-phen ylglycine; 200 mu M) completely inhibited the 1S,3R ACPD-induced reduc tion in paired pulse depression but was without effect on the L-AP4 re sponse. The relatively specific group II antagonist MCCG ((2S,3S,4S)-2 -methyl-2-carboxy cycloproprylglycine) at 200 mu M and 500 mu M, atten uated but did not completely inhibit the DCG-IV induced reduction of p aired pulse depression. The putative group III pre-synaptic mGlu recep tor antagonist alpha-methyl-L-AP4 and MSOP ((RS)-alpha-methylserine-O- phosphate) both at 200 mu M inhibited the L-AP4-induced reduction in p aired pulse depression at intermediate phase interstimulus intervals b ut not at early interstimulus intervals. These results specifically de monstrate the involvement of group II and III mGlu receptor ligands in the modulation of paired pulse depression in the medial perforant pat hway. (C) 1997 Elsevier Science B.V.