PRESYNAPTIC INHIBITORY-ACTION OF THE GROUP-II METABOTROPIC GLUTAMATE-RECEPTOR AGONISTS, LY354740 AND DCG-IV

Electrophysiological studies were carried out on the presynaptic inhib itory action of the group II metabotropic glutamate (mGlu) receptor ag onists (+)-2-aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740 ) and 1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) in t hree paths of the rat hippocampus, the medial and lateral perforant pa th to the dentate gyrus, and the Schaffer collateral/commissural path to CA1. LY354740 caused a dose-dependent reversible inhibition of the field excitatory postsynaptic potential (EPSP) in the medial and later al perforant paths, with an EC50 of 115 +/- 16 nM and 230 +/- 58 nM, r espectively. Maximal inhibition by LY354740 was much greater in the me dial path (about 80%) than in the lateral path (about 50%). No inhibit ion was observed in CA1. A presynaptic inhibition was confirmed by LY3 54740 inducing dose-dependent changes in paired-pulse depression/facil itation. DCG-IV had a similar action to LY354740, but with a lower pot ency. (C) 1998 Elsevier Science B.V. All rights reserved.