Seizure activity and changes in hippocampal extracellular glutamate, GABA, dopamine and serotonin

Abstract

Increases in hippocampal extracellular neurotransmitter levels have consistently been observed during temporal lobe seizures in humans, but animal studies on this subject have yielded conflicting results. Our aim was to better characterise the relationship between seizure activity and changes in hippocampal glutamate, GABA, dopamine and serotonin by comparing three limbic seizure models which differ only in the pharmacological mechanism used to induce seizures. Seizures were evoked in freely moving rats by intrahippocampal microperfusion, via a microdialysis probe, of the muscarinic receptor agonist pilocarpine (10mM), GABA(A) receptor antagonist picrotoxin (100microM) or group I metabotropic glutamate receptor agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) (1mM). Seizure-related behavioural changes were scored and hippocampal extracellular glutamate, GABA, dopamine and serotonin concentrations were monitored. Seizures were of comparable severity in all groups. During seizures, hippocampal glutamate, GABA and dopamine concentrations increased in all groups. Glutamate increases were significantly higher in the picrotoxin group. Hippocampal serotonin concentration increased following pilocarpine and picrotoxin, but not DHPG. Our results suggest a direct relationship between seizure activity and increased hippocampal extracellular concentrations of glutamate, GABA and dopamine, but not serotonin. The fact that picrotoxin induces seizures by disinhibition, rather than direct excitation, may account for the larger glutamate increases in this group.