title: Temporal lobe epileptiform activity following systemic administration of 4-aminopyridine in rats.
abstract: OBJECTIVE
  The K(+) channel blocker 4-aminopyridine (4AP) induces epileptiform synchronization in brain slices maintained in vitro without interfering with γ-aminobutyric acid (GABA)A receptor-mediated inhibition and, actually, even enhancing it. The hypothesis that similar electrographic epileptiform patterns occur in vivo following systemic 4AP injection was tested here.
  
  
  METHODS
  Sprague-Dawley rats (n = 13) were implanted with bipolar electrodes aimed at the hippocampal CA3 region, entorhinal cortex, subiculum, dentate gyrus, and amygdala. They were then injected with a single dose of 4AP (4-5 mg/kg, i.p.), and video-monitoring/electroencephalography (EEG) recordings were performed.
  
  
  RESULTS
  4AP induced convulsive or nonconvulsive seizures in 12 of 13 rats, along with generalized fascicular twitching, wet-dog shakes, and myoclonic jerks. On EEG, we observed in 7 (58.3%) of 12 animals long-lasting interictal spikes from the subiculum before the occurrence of the first seizure. Once seizures had started, interictal spikes occurred in all areas with no fixed site of origin. Most seizures (41/60, 68.3%) were characterized by a low-voltage fast-activity onset pattern and were convulsive (48/60, 80%). 4AP also induced highly rhythmic theta (6-11 Hz) oscillations in CA3 and entorhinal cortex before seizure occurrence.
  
  
  CONCLUSIONS
  Our study shows that systemic 4AP administration in vivo can enhance theta oscillations and induce slow interictal spikes and low-voltage fast-onset seizures similar to those reported in brain slices. We propose that these effects may reflect, at least in part, enhanced GABAA receptor-mediated inhibition as reported in in vitro studies.
authors.affiliation: Montreal Neurological Institute and Department of Neurology & Neurosurgery, McGill University, Montréal, Quebec, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lévesque
authors.forename: Pariya
authors.initials: P
authors.lastname: Salami
authors.forename: Charles
authors.initials: C
authors.lastname: Behr
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D056654:CA3 Region, Hippocampal / Q000187:drug effects; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000139:chemically induced / Q000523:psychology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced* / Q000503:physiopathology* / Q000523:psychology; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology; D007274:Injections, Intraperitoneal; D026902:Potassium Channel Blockers / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013826:Theta Rhythm
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine