Liraglutide chronic treatment prevents development of tolerance to antiseizure effects of diazepam in genetically epilepsy prone rats

Glucagon-like peptide-1 (GLP-1) is a hormone that can regulate several neuronal functions. The modulation of GLP-1 receptors emerged as a potential target to treat several neurological diseases, such as epilepsy. Here, we studied the effects of acute and chronic treatment with liraglutide (LIRA), in genetically epilepsy prone rats (GEPR-9s). We have also investigated the possible development of tolerance to antiseizure effects of diazepam, and how LIRA could affect this phenomenon over the same period of treatment. The present data indicate that an acute treatment with LIRA did not diminish the severity score of audiogenic seizures (AGS) in GEPR-9s. By contrast, a chronic treatment with LIRA has shown only a modest antiseizure effect that was maintained until the end of treatment, in GEPR-9s. Not surprisingly, acute administration of diazepam reduced, in a dose dependent manner, the severity of the AGS in GEPR-9s. However, when diazepam was chronically administered, an evident development of tolerance to its antiseizure effects was detected. Interestingly, following an add-on treatment with LIRA, a reduced development of tolerance and an enhanced diazepam antiseizure effect was observed in GEPR-9s. Overall, an add-on therapy with LIRA demonstrate benefits superior to single antiseizure medications and could be utilized to treat epilepsy as well as associated issues. Therefore, the potential use of GLP1 analogs for the treatment of epilepsy in combination with existing antiseizure medications could thus add a new and long-awaited dimension to its management.

Automated summary

The hormone GLP-1 has been identified as a potential target for the treatment of neurological diseases such as epilepsy. In this study, the effects of acute and chronic treatment with LIRA on epilepsy-prone rats were investigated. It was found that chronic treatment with LIRA had a modest antiseizure effect, while acute treatment did not show significant results. Additionally, chronic use of diazepam led to the development of tolerance, but when combined with LIRA, a reduced development of tolerance and an enhanced antiseizure effect were observed. Overall, LIRA as an add-on therapy showed superior benefits compared to single antiseizure medications in treating epilepsy.