The effects of maximal electroshock, used as a model of
generalized seizures, were studied on extracellular
GABA and
glutamate levels in the ventral hippocampus of the freely-moving rat, using in vivo microdialysis. Following a maximal electroshock there was a rapid decline in
GABA levels (46 +/- 5%) in the 20 min immediately after the seizure and levels remained depressed for a further 60 min. However, although there was a transient small decrease (11 +/- 2%) in
glutamate levels in the first 20 min post-ictally, there followed a more prolonged, larger increase in the next 40 min. Maximal electroshock, administered in the absence of extracellular
calcium, did not change
GABA levels, while
glutamate levels were again increased (42 +/- 8%) in the 40-80 min after the
shock. Local perfusion with
nickel (1 mM) to block
T-type calcium channels had no effect on basal
GABA or
glutamate levels but prevented maximal electroshock-induced changes in both
amino acids. Experiments were carried out to test the hypothesis that the post-ictal increased
glutamate release was due to the decrease in
GABA release. Perfusion with the potent
GABA re-uptake inhibitor
NNC-711, for 60 min prior to administration of maximal electroshock, increased
GABA levels (436 +/- 58%) and abolished the seizure-induced decrease. Basal
glutamate levels were not affected by perfusion with
NNC-711 but subsequent maximal electroshock also failed to affect levels. Local perfusion with the GABAA receptor antagonist
bicuculline (1, 10 and 100 microM) had no effect on basal
GABA levels but
glutamate levels were increased (46 +/- 5%) after perfusion with 100 microM
bicuculline.(ABSTRACT TRUNCATED AT 250 WORDS)