Alpha-2a Adrenergic Receptor (Α2ar) Activation in Genetic Absence Epilepsy: An Absence Status Model?

Abstract

BACKGROUND AND PURPOSE: The updates in the definition of absence status epilepticus raise questions about the pathophysiological aspects of absence status. Here, we propose an animal model of absence status epilepticus, induced by specific alpha 2a adrenergic receptor (α2AR) activation. EXPERIMENTAL APPROACH: An α2AR agonist, dexmedetomidine was injected intracerebroventricularly into the adult rats with genetic absence epilepsy and the electroencephalography (EEG) from animals was recorded. The total duration, number and mean duration of each spike-and-wave discharges (SWDs) were evaluated. The blocks of absence status events were classified as first and second set of absence statuses. Ethosuximide was given as a pre-treatment to another group of animals, later injected with 2.5 μg dexmedetomidine. Power spectral characteristics and coherence analysis for the absence status events and sleep were performed on the EEG. KEY RESULTS: The 2.5 µg dose of dexmedetomidine increased the total SWD duration and induced continuous SWDs up to 26 min. Following a first absence status event, sleep is induced and it was followed by the second set of absence status events. Ethosuximide pre-treatment blocked the occurrence of these events. Power spectral density analyses revealed that dexmedetomidine injection-induced absence seizures and the absence seizures following sleep had lower spectral power than typical SWDs in the frequency bands. CONCLUSIONS AND IMPLICATIONS: This study presents that activation of α2AR may induce absence status epilepticus and this can be an animal model to study the pathophysiological role of absence status. Our results strengthen the significant role of α2AR in SWD generation or termination.