An increase in the release of
excitatory amino acids has consistently been observed in the hippocampus during
seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of
glutamate and
aspartate during epileptogenesis and in the interictal chronic period of established
epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal
glutamate and
aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental
temporal lobe epilepsy, using in vivo microdialysis. Hippocampal extracellular
glutamate and
aspartate levels were evaluated: 24h after
pilocarpine-induced
status epilepticus (SE); during the latency period preceding spontaneous
seizures; immediately after the first spontaneous seizure; in the chronic (epileptic) period. We found that (i) basal (spontaneous)
glutamate outflow is increased in the interictal phases of the chronic period, whereas basal
aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased
glutamate and
aspartate outflow in both control and
pilocarpine-treated animals, and the overflow of
glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent
seizures. Together with an impairment of
GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state.