Decreased sensitivity to Group III mGluR agonists in the lateral perforant path 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 dentate 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 dps). L-SOP was more potent in controls than kindled or 28 dps animals, decreasing the fEPSP slope with IC50s of 2.4 microM, 18.7 microM and 10.5 microM, respectively. Paired pulse facilitation (PPF, 50 ms) was comparable in control and kindled rats, but was markedly reduced in 28 dps rats, indicating increased release probability. Inhibition of the field excitatory postsynaptic potentials (fEPSP) by L-SOP was correlated with enhanced PPF in all groups, affirming a presynaptic site of action. At moderate levels of L-SOP-induced 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 (probably mGluR8) response in the LPP after kindling. Furthermore, PPF changes indicate that the kindled state may be associated with a long-lasting increase in the probability of release from LPP terminals, which may be temporarily masked or counterbalanced by recent seizures.
Klapstein
G J
GJ
Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095-1769, USA.
Meldrum
B S
BS
Mody
I
I
D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000378:metabolism*; D008297:Male; D019580:Perforant Pathway / Q000187:drug effects / Q000378:metabolism*; D010768:Phosphoserine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; C120877:methylserine phosphate; D010768:Phosphoserine