Exendin-4 increases absence-like seizures and anxiety-depression-like behaviors in WAG/Rij rats

Aim: Epilepsy is a neurological condition affecting millions of people worldwide. Glucagon-like peptide-1 (GLP-1) is a gut hormone, and its neuroprotective effect was investigated in previous studies. In this study, the effects of exendin-4, a GLP-1 receptor agonist, were studied in genetic absence epileptic Wistar Albino Glaxo/Rijswijk rats (WAG/Rij). WAG/Rij rat is a genetic model of the absence epilepsy and depression-like comorbidity. Method: We examined the effects of exendin-4 (10, 50 and 100 mg/kg) on the absence seizures (Electrocorticography [ECoG] recordings), anxiety level (open-field test [OF]), and depression-like levels (forced swimming test [FST]) in the WAG/Rij rats. Basal ECoG recording was performed for all rats. Then, exendin-4 (10, 50 or 100 mg/kg) was administered intraperitoneally and ECoG recording was made for 180 min. After ECoG recording, forced swimming test and open-field test were applied. Results: Administration of 10, 50, or 100 mg/kg exendin-4 increased the duration and number of spike wave discharges (SWDs) considerably without changing the amplitude. The 100 mg/kg dose of exendin4 was the most effective in increasing the total duration of SWDs. Additionally, all exendin-4 doses increased anxiety level in OF and depression-like level in FST. Conclusion: Our results showed that exendin-4 increased SWD incidence and anxiety-and depression like behaviors in the WAG/Rij rats. Besides, it was also found that high doses caused the most proabsence effect. (c) 2021 Elsevier Inc. All rights reserved.