Effects of Diazepam and Ketamine on Pilocarpine-Induced Status Epilepticus in Mice

Status epilepticus (SE) is a life-threatening condition needing immediate care to prevent brain damage. SE with electrographic and behavioral features similar to those seen in humans is reproduced in rodents by i.p. pilocarpine injection, and can be terminated by diazepam and ketamine treatment but only behaviourally, not electrographically. Little is known on the behavioral and EEG effects induced by a delayed administration of ketamine (25 mg/kg) after diazepam (10 mg/kg) or vice versa. Therefore, we analysed behavior and EEG activity recorded from the mouse hippocampal CA3 region before, during SE and after anticonvulsant treatments. In the first group (n = 4), diazepam was administered one hour before ketamine whereas in the second group (n = 4) ketamine was administered one hour before diazepam. The EEG SE did not disappear after each of the two treatments but progressed within 4 h to a pattern of interictal discharges. However, diazepam administration before ketamine significantly shortened the time of behavioral recovery compared to when ketamine was administered before diazepam (p < 0.05). The two protocols were also associated to distinct EEG changes in gamma and high frequency oscillations. In conclusion, although diazepam and ketamine are not effective in stopping EEG SE, diazepam administration one hour before ketamine shortens behavioral recovery in pilocarpine-treated mice.