Seizures induced by GABAB-receptor blockade in early-life induced long-term GABA(B) receptor hypofunction and kindling facilitation.
Consequences of seizures in the developing brain are not completely understood. The aim of this study was to investigate the long-term alterations of synaptic transmission and seizure susceptibility in the hippocampus after early-life seizures induced by systemic injection of a GABA(B)-receptor antagonist CGP56999A in immature rats. Experimental rats were injected with CGP56999A 1-1.5mg/kg intraperitoneally (i.p.) on postnatal day 15, while controls were injected with saline i.p. Seizures induced by CGP56999A originated mostly from the hippocampus and amygdala, and were associated with no mortality. Thirty days after seizures, laminar field potentials were recorded in the hippocampus in urethane-anesthetized rats by 16-channel silicon probes and analyzed as current source density. As compared to early-life saline-injected rats, early-life CGP56999A-induced seizure rats showed a significant decrease in paired-pulse inhibition of population spikes at 150-400 ms interpulse intervals (IPIs) in CA1, following CA3 stimulation, and at 400 ms IPI in the dentate gyrus, following medial perforant path stimulation. In a separate experiment, adolescent rats that experienced CGP56999A-induced early-life seizures showed a robust facilitation of hippocampal kindling, as compared to saline controls. In conclusion, seizures induced by GABA(B)-receptor blockade in immature rats resulted in a long-lasting loss of GABA(B)-receptor mediated paired-pulse inhibition in CA1 and dentate gyrus, which may contribute to the increase of seizure susceptibility in the hippocampus.
Tsai
Min-Lan
ML
Program in Neuroscience, University of Western Ontario, London, Ontario, Canada.
Shen
Bixia
B
Leung
L Stan
LS
D000465:Algorithms; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018891:Dentate Gyrus / Q000502:physiology; D018450:Disease Progression; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D004594:Electrophysiology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000502:physiology; D007276:Injections, Intraventricular; D007696:Kindling, Neurologic / Q000187:drug effects*; D010721:Phosphinic Acids / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000139:chemically induced*
C102659:CGP 56999A; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids