Comparison of short-term effects of midazolam and lorazepam in the intra-amygdala kainic acid model of status epilepticus in mice.
Benzodiazepines remain as the first-line treatment for status epilepticus (SE), but debate continues as to the choice and delivery route of pharmacotherapy. Lorazepam is currently the preferred anticonvulsant for clinical use, but midazolam has become a popular alternative, particularly as it can be given by nonintravenous routes. Anticonvulsants are also commonly used to terminate SE in animal models. Here, we aimed to compare the efficacy of midazolam with that of lorazepam in an experimental model of focal-onset SE. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in 8week old C57Bl/6 mice. Forty minutes later, mice were treated with an intraperitoneal injection of either lorazepam or midazolam (8mg/kg). Electroencephalogram (EEG) activity, histology, and behavioral tests assessing recovery of function were evaluated and compared between groups. Intraperitoneal injection of either lorazepam or midazolam resulted in similar patterns of reduced EEG epileptiform activity during 1-hour recordings. Damage to the hippocampus and presentation of postinsult anxiety-related behavior did not significantly differ between treatment groups at 72h. However, return of normal behaviors such as grooming, levels of activity, and the evaluation of overall recovery of SE mice were all superior at 24h in animals given midazolam compared with lorazepam. Our results indicate that midazolam is as effective as lorazepam as an anticonvulsant in this model while also providing improved animal recovery after SE. These data suggest that midazolam might be considered by researchers as an anticonvulsant in animal models of SE, particularly as it appears to satisfy the requirements of refining procedures involving experimental animals at early time-points after SE.
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Mairead
M
Diviney
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
James P
JP
Reynolds
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland. Electronic address: dhenshall@rcsi.ie.
David C
DC
Henshall
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007608:Kainic Acid / Q000633:toxicity*; D008140:Lorazepam / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008874:Midazolam / Q000494:pharmacology / Q000627:therapeutic use*; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D000927:Anticonvulsants; D001569:Benzodiazepines; D008140:Lorazepam; D008874:Midazolam; D007608:Kainic Acid
3Rs (Replacement, Refinement, Reduction); Animal welfare; Anticonvulsants; Behavior; Midazolam; Status epilepticus