Diazepam terminates brief but not prolonged seizures in young, naive rats

Purpose: Ample evidence exists from both clinical and animal studies that the success of benzodiazepine intervention during status epilepticus (SE) in the mature nervous system is inversely related to seizure duration. This relationship has not been well studied in the developing nervous system. Methods: The objective of this study was to investigate the relation of age and success of diazepam (DZP) treatment in the lithium-pilocarpine model of secondarily generalized seizure in the rat by using naive rats of three age groups, roughly corresponding to the human ages of infancy (P15), adolescence (P20), and adult (P60). Results: In all age groups, the dosage of DZP that stopped the seizures at 5 min was not effective in terminating seizures at 60 min. This decline in efficacy was present as early as 15 min after seizure onset. Conclusions: These findings demonstrate that the inverse relation between the success of benzodiazepine intervention and seizure duration is observed in young as well as in adult rats and provide further evidence that intervention for SE should commence early.