Premium
Temporal lobe epileptiform activity following systemic administration of 4‐aminopyridine in rats
Author(s) -
Lévesque Maxime,
Salami Pariya,
Behr Charles,
Avoli Massimo
Publication year - 2013
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12041
Subject(s) - subiculum , ictal , entorhinal cortex , hippocampal formation , dentate gyrus , neuroscience , hippocampus , 4 aminopyridine , electroencephalography , convulsion , electrophysiology , medicine , epilepsy , psychology , potassium channel
Summary Purpose: 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. Key Findings: 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. Significance: 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 GABA A receptor–mediated inhibition as reported in in vitro studies.