Decreased sensitivity to Group III mGluR agonists in the lateral perforantpath following kindling

The ability of the selective Group III mGluR agonist L-serine-O-phosphate ( L-SOP) to inhibit lateral perforant path (LPP) evoked responses in the dent ate gyrus was tested in hippocampal slices from commissurally-kindled rats 1-2 days after the last seizure, implanted controls, and fully-kindled rats rested for 28 days without stimulated seizures (28 days post-seizure, 28 d ps). L-SOP was more potent in controls than kindled or 28 dps animals, decr easing the fEPSP slope with IC(50)s of 2.4 mu M, 18.7 mu M and 10.5 mu M, r espectively. Paired pulse facilitation (PPF, 50 ms) was comparable in contr ol and kindled rats, but was markedly reduced in 28 dps rats, indicating in creased release probability. Inhibition of the field excitatory postsynapti c potentials (fEPSP) by L-SOP was correlated with enhanced PPF in all group s, affirming a presynaptic site of action. Ar moderate levels of L-SOP-indu ced inhibition (20-60%), PPF showed significantly greater enhancement in 28 dps than in the other two groups. These results are interpreted as showing a functional reduction of the presynaptic inhibitory Group III mGluR (prob ably mGluR8) response in the LPP after kindling. Furthermore, PPF changes i ndicate that the kindled state may be associated with a long-lasting increa se in the probability of release from LPP terminals, which may be temporari ly masked or counterbalanced by recent seizures. (C) 1999 Elsevier Science Ltd. All rights reserved.