BackgroundNodding syndrome (NS) is one type of epilepsy and a progressive disease characterized by nodding symptoms with children in sub-Saharan Africa. The burden for NS children is heavy, not only mentally but financially for themselves and their families, and yet, the cause and cure of NS remain unknown. The kainic acid-induced model in experimental animals is a well-known epilepsy model that is useful for studying human diseases. In this study, we examined similarities of clinical symptoms and histological brain changes between NS patients and kainic acid-treated rats. In addition, we argued for kainic acid agonist as one of the causes of NS.MethodsClinical signs in rats were studied after kainic acid administration, and histological lesions including the expression of tau protein and gliosis, were examined at 24 h, 8 days, and 28 days after dosing.ResultsKainic acid-induced epileptic symptoms were observed in rats, including nodding accompanied by drooling and bilateral neuronal cell death in the hippocampus and piriform cortex regions. In the regions that exhibited neuronal cell death, an increase in tau protein expression and gliosis were found immunohistochemically. The symptoms and brain histology were similar in the NS and kainic acid-induced rat models.ConclusionThe results suggest that kainic acid agonist may be one of the causative substances for NS.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41182-023-00520-0.