Fig. 1

Time course of behavioral state and PTZ seizure threshold in rats given EtOH by gavage. a. Cartoon representation of behavioral state over time after administration of EtOH by oral intubation (gavage) in rat. EtOH exhibits maximum absorption into the brain by ~2 h, accompanied by behavioral depression. As the EtOH leaves the brain, activity (arbitrary units, amplitude depends on dose) returns to normal. Before the EtOH is even eliminated, the behavioral activity returns to normal and overshoots to produce a rebound hyperexcitability (withdrawal), then returns to normal by 24 h (blue diamonds). CIE after 5 doses (pink squares), reduces initial depression (tolerance) and slows return to normal with heightened severity of rebound hyperexcitability. After 60 doses (open triangles) in rats (30 in mice) the heightened withdrawal does not return to normal and stays elevated for at least 40–120 days, possibly for life [109]. This is the CIE ‘kindled’ state. b. Effect of CIE on PTZ seizure threshold: persistent decrease after cessation of EtOH treatment. EtOH, 5.0 g/kg/48 h, was given by oral intubation; PTZ seizure threshold was measured 18 h after EtOH. CIV rats tested at the same times as the CIE rats showed no significant changes in PTZ seizures. Horizontal bars indicate mean PTZ seizure threshold. ** p < 0.01. Reproduced from Kokka et al. (1993) [109] with permission. * p < 0.05