title: Decreased GABA release following tonic-clonic seizures is associated with an increase in extracellular glutamate in rat hippocampus in vivo.
abstract: 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)
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D004597:Electroshock; D004830:Epilepsy, Tonic-Clonic / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009532:Nickel / Q000494:pharmacology; D009539:Nicotinic Acids / Q000494:pharmacology; D009557:Nipecotic Acids; D010091:Oximes / Q000494:pharmacology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D000927:Anticonvulsants; D018756:GABA Antagonists; D009539:Nicotinic Acids; D009557:Nipecotic Acids; D010091:Oximes; C078793:NNC 711; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D009532:Nickel; D002118:Calcium; D001640:Bicuculline