Considering the contribution of hippocampal formation and
glutamate-mediated signalling to epileptogenesis, we investigated the effects of group III
metabotropic glutamate receptor (mGluR)-selective
ligands on the kindling of
seizures. We also examined the concentration of the
amino acid glutamate,
GABA,
alanine and
taurine in the hippocampus of rats using a microdialysis technique.
Pentylenetetrazol (PTZ), a non-competitive antagonist of the
GABA(A) receptor, was administered intraperitoneally at 35 mg/kg
body weight to induce
seizures. It was determined that the kindling of PTZ-induced
seizures could be attenuated by post intracerebroventricular administration of 100 nmol of the group III mGluR antagonist CPPG [(RS)-a-cyclopropyl-4-phosphonophenylglycine]. There were significant differences in tested parameters during the final stages of the kindling procedure. The group III mGluR agonist
L-AP4 [L-(+)-2-amino-4-phosphonobutyric
acid at 100 nmol, i.c.v.] did not significantly affect the kindling of
seizures in comparison to control rats, although there was acceleration of the process as compared to CPPG treated animals. We demonstrated that the baseline concentrations of
glutamate,
GABA,
alanine,
taurine, and the
glutamine/
GABA ratio were elevated in the hippocampus of fully kindled rats. Intracerebroventricular administration of a single dose of CPPG increased the concentrations of
glutamate in the hippocampus of control, non-kindled rats. Intracerebroventricular administration of
L-AP4 did not affect the hippocampal
amino acid concentration in either animal group. Overall, these data suggest that there is a shift in the balance between
neurotransmitters towards increased production of
excitatory amino acids, and this may be mediated by group III mGluRs during seizure kindling.