A behavioral and electrocorticographic comparison of diazepam and pentylenetetrazol in rat pups

This experiment assessed the possibility suggested by previous research that benzodiazepines cause convulsions in infant rats. Seven-day-old Wistar rats were randomly assigned to receive either diazepam (DZP) (0, 0.5 or 2.5 mg/kg), the convulsogen pentylenetetrazol (PTZ) (50 mg/kg), or DZP followed 30 minutes later by PTZ. The amount of paddling and wall progression and head and body tremors was recorded for each group. Both DZP and PTZ elevated paddling and wall progression, but only PTZ elevated head and body tremor scores. DZP antagonized the PTZ-induced increases in head and body tremors. In a second experiment, seven-day-old pups were implanted with cortical electrodes. The following day, baseline electrocorticograms (ECoGs) were taken for each animal. Each pup subsequently received either DZP vehicle, 0.5 mg/kg DZP, 50 mg/kg PTZ, or 0.5 mg/kg DZP followed 30 minutes later by 50 mg/kg PTZ. Neither the vehicle nor the DZP injections altered ECoG activity. In contrast, PTZ-treated pups showed continuous, high-amplitude, spiking activity. Pretreatment with DZP eliminated these PTZ-induced alterations in ECoG activity. We conclude that in infant rats, the behavioral and electrophysiological effects of DZP and PTZ are distinct from one another. Furthermore, both the behavioral and the electrocorticographic effects of PTZ are blocked by DZP. It is unlikely that DZP causes seizures in neonatal rats.