The optimization of experimental models mediated by impaired gabaergic neurotransmission

Relevance. Epilepsy is one of the most common neurological diseases, which is based on a disregulation of the balance between excitatory and inhibitory neurotransmission in the central nervous system. In this regard, the optimization of conditions for the currently used seizure models that reflect the pathophysiology of epilepsy, for the evaluation of the efficacy of potential drugs, remains a relevant task in experimental pharmacology. Objective. Optimization of the conditions of three experimental seizure models induced by intravenous administration of convulsants with different mechanisms of action for subsequent pharmacological evaluation of anticonvulsant and pro-convulsive activities. Materials and methods. Epilepsy was induced in ICR mice by intravenous administration of pentylenetetrazol, bicuculline, or picrotoxin into the lateral tail vein at a constant rate. The seizure threshold was determined as the minimum dose of convulsants. Clonic seizures, generalized clonic seizures, and generalized tonic seizures were recorded using a video camera with subsequent evaluation. Results. Based on the experimental results, optimal administration parameters were established for models of pentylenetetrazole, bicuculline, and picrotoxin-induced seizures, ensuring reproducibility and sensitivity to anticonvulsants. The optimality of the convulsant administration conditions for the models is confirmed by the demonstration of a dose-dependent anticonvulsant effect of diazepam, which statistically significantly increases the seizure threshold and slows the development of a seizure in all models. Conclusion. As a result of this study, the optimal conditions for the administration of convulsants with different mechanisms of action were determined for three experimental seizure models. The obtained results can be used for subsequent preclinical studies of potential compounds possessing anticonvulsant activity.