A model of atypical absence seizures - EEG, pharmacology, and developmental characterization

Objective and background: Atypical absence seizures differ markedly from ty pical absence seizures in EEG findings, ictal behavior, and neurodevelopmen tal outcome. The object of these experiments was to provide electrical, beh avioral, pharmacologic, and developmental characterization of a putative an imal model of atypical absence seizures. Methods: Atypical absence seizures were induced in Long Evans hooded rats by treatment with a cholesterol bio synthesis inhibitor, AY-9944 (AY), during development. Prolonged video EEG recordings were made from chronically implanted depth electrodes in the wak ing and sleep states in adult and developing animals during and after AY tr eatment. Also, the response of AY-induced atypical absence seizures to drug s known to exacerbate and block typical absence seizures was ascertained. R esults: AY treatment resulted in spontaneous, bilaterally synchronous, slow spike-and-wave discharges (SWD), which were frequent, recurrent, prolonged , and lifelong. SWD began as early as postnatal day 21, occurred throughout all stages of sleep, and were associated with myoclonic jerks during sleep . The SWD were significantly prolonged by carbamazepine, gamma -hydroxybuty rate, and the gamma -aminobutyrate type B (GABA(B)) receptor (GABA(B)R) ago nist baclofen. AY-induced seizures were abolished by diazepam, ethosuximide , and the GABA(B)R antagonist CGP 35348 but returned as the drugs were elim inated. Atypical features of absence seizures in this model are slow spike- wave, emanation of SWD from hippocampus, gradual onset and offset of ictal behavior, and the ability of the animals to move during the spike-and-wave bursts. Conclusion: The AY-treated rat represents a predictable, reproducib le, and clinically relevant animal model of atypical absence seizures that may be used to investigate the pathogenesis and treatment of this malignant disorder.