Electrographic and behavioral indices of ethanol withdrawal sensitization

Behavioral and electrographic measures of CNS hyperexcitability were studied in separate groups of mice undergoing multiple ethanol (EtOH) withdrawals in a well-characterized model of EtOH withdrawal sensitization. Consistent with previous studies from this laboratory, mice experiencing repeated cycles of EtOH intoxication and withdrawal exhibited significantly more severe withdrawal seizures (handling-induced convulsions, HIC) in comparison to animals tested following a single withdrawal episode. Spontaneous EEG data collected from a separate group of mice undergoing the same EtOH exposure regimen exhibited a highly-typified alteration during EtOH withdrawal wherein normal EEG was abruptly replaced with high-voltage, repetitive spikes in a frequency range of seven to nine spikes per second. This paroxysmal EEG data, termed ‘brief spindle episodes’ (BSE) was virtually absent at baseline (prior to EtOH exposure). However, following withdrawal from chronic EtOH exposure, the percent of the EEG recordings containing BSE increased significantly in a time dependent manner. Moreover, in mice undergoing multiple cycles of EtOH exposure and withdrawal, BSE activity progressively increased over successive withdrawal cycles. In contrast, mice tested after repeated cycles of similar handling in the absence of EtOH exposure did not exhibit significant BSE activity until experiencing their one and only EtOH withdrawal episode. Thus, both behavioral and electrographic signs of EtOH withdrawal-related CNS hyperexcitability increased in magnitude during the course of each withdrawal cycle as well as progressively intensifying over successive withdrawal cycles.