Behavioral alterations in a mouse model of temporal lobe epilepsy induced by intrahippocampal injection of kainate

Abstract

Patients with temporal lobe epilepsy are frequently afflicted with psychiatric comorbidity and deficits in spatial and other forms of declarative memory. The relationship between epilepsy and psychopathology is poorly understood, so that systematic research in this area is important. In the present study, we characterized various behaviors and learning and memory in a mouse model in which major aspects of mesial temporal lobe epilepsy can be reproduced. In this model, a single unilateral injection of kainate into the dorsal hippocampus induces a nonconvulsive status epilepticus, followed by development of spontaneous recurrent seizures and ipsilateral lesions of CA1, CA3c and dentate hilus neurons. Unexpectedly, the epileptic mice exhibited only few alterations in a behavioral test battery used to investigate locomotor activity and function, emotionality, depression-related behavior and learning and memory. In contrast to recent experiments with the same test battery in epileptic mice generated by systemic administration of pilocarpine, mice with focal kainate administration did not exhibit reduced explorative behavior or increases of anxiety-related behavior. However, similar to pilocarpine-treated mice, a decrease in depression-like behavior was observed in the forced swimming test. In the Morris water maze test, kainate-treated animals exhibited retarded acquisition and impaired retention of visual-spatial information. Our data suggest that the focal kainate model of mesial temporal lobe epilepsy may contribute to understanding the neurobiological mechanisms underlying the association between epilepsy and behavioral or cognitive alterations.