Decrease of hippocampal GABA B receptor-mediated inhibition after hyperthermia-induced seizures in immature rats.
OBJECTIVE
Whether febrile seizures have detrimental consequences on the brain is still controversial. We hypothesized that neuronal inhibition in the hippocampus is altered after hyperthermia-induced seizures in immature rats.


METHODS
Rats were given a single seizure by a heat lamp on postnatal day (PND) 15, or repeated seizures by heated air on PND 13 to 15. Fourteen or 30 days after the seizure(s), laminar field potentials were recorded by 16-channel silicon probes in CA1 and the dentate gyrus (DG), in response to the paired-pulse stimulation of the CA3 and medial perforant path, and analyzed as current source density. Gamma-aminobutyric acid (GABA)(B)-receptor antagonist CGP35348 was injected intracerebroventricularly (icv).


RESULTS
At 14 but not at 30 days after a single or after repeated hyperthermia-induced seizures, paired-pulse facilitation (PPF) of the CA1 population spikes at 100 to 200 ms interpulse intervals (IPIs) was significantly increased in seizure as compared with control rats, irrespective of the types of induced seizures. CGP35348 icv also resulted in PPF at 100 to 200 ms IPIs in CA1 of control rats, but CGP35348 had no effect on PPF in seizure rats. At 30 days after repeated seizures, paired-pulse inhibition in the DG was significantly increased at 30-ms IPI, and PPF was increased at 200-ms IPI. CGP35348 increased paired-pulse inhibition in the DG in repeated-seizure rats but not in control rats.


CONCLUSIONS
We conclude that hyperthermia-induced seizures in immature rats induced a decrease of GABA(B) receptor-mediated inhibition in CA1 and DG that lasted > or =14 to 30 days after hyperthermic seizure(s).
Tsai
Min-Lan
ML
Program in Neuroscience, University of Western Ontario, London, Ontario, Canada N6A 5C2.
Leung
L Stan
LS
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005334:Fever / Q000150:complications / Q000378:metabolism*; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007276:Injections, Intraventricular; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology; D019580:Perforant Pathway / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans / Q000254:growth & development; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D003294:Seizures, Febrile / Q000209:etiology / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C066430:CGP 35348