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A behavioral and electrocorticographic comparison of diazepam and pentylenetetrazol in rat pups
J W Smythe1, C L Ryan, B A Pappas
1Department of Psychology, Carleton University, Ottawa, Ontario, Canada.
Insights
This study investigated if diazepam (DZP) causes seizures in infant rats. Results show DZP did not cause convulsions or alter electrocorticograms, suggesting it does not induce seizures in neonatal rats.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Previous research suggested benzodiazepines might induce convulsions in infant rats.
- Understanding drug effects in neonatal models is crucial for safety and efficacy.
Purpose of the Study:
- To determine if diazepam (DZP) causes seizures in seven-day-old Wistar rats.
- To differentiate the effects of DZP from the known convulsogen pentylenetetrazol (PTZ).
Main Methods:
- Two experiments were conducted on seven-day-old Wistar rats.
- Behavioral assessments (paddling, tremors) and electrocorticograms (ECoGs) were recorded after administration of DZP, PTZ, or both.
- DZP was administered at 0, 0.5, or 2.5 mg/kg; PTZ at 50 mg/kg.
Main Results:
- Both DZP and PTZ increased paddling and wall progression.
- Only PTZ significantly increased head and body tremors.
- DZP antagonized PTZ-induced tremors and eliminated PTZ-induced spiking activity on ECoGs.
- DZP alone did not alter ECoG activity.
Conclusions:
- Diazepam (DZP) and pentylenetetrazol (PTZ) exhibit distinct behavioral and electrophysiological effects in infant rats.
- DZP does not appear to cause seizures in neonatal rats.
- DZP antagonizes the pro-convulsant effects of PTZ in this model.
Abstract:
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.