Abstracts

The lithium-pilocarpine (li-pilo) model of epilepsy is characterized by occurrence of spontaneous recurrent seizures (SRS) originating in a hyperexcitable circuit generated by the extensive lesions induced by status epilepticus (SE). These are mainly located in hippocampus, parahippocampal cortices, amygdala and thalamus. Many of these structures, also lesioned in humans, are involved in cognitive functions and anxiety and impact on patients quality of life. Here, we explored the performance of adult rats rendered epileptic by li-pilo SE in behavioral tasks reflecting spatial working memory, anxiety and object recognition. 11 adult male rats survived li-pilo SE and 11 control rats received lithium and saline (li-saline rats). Li-pilo rats were observed until the occurrence of the first SRS and studied at 4-5 months later. Spatial working memory was tested in an eight-arm maze, anxiety in an elevated plus-maze and object recognition in a standard size cage. Neurons were counted on thionine brain sections obtained from the 22 animals sacrificed after the behavioral testing. In the elevated plus-maze, li-pilo rats entered more often and spent more time than li-saline rats in open arms, and made far more head-dips. In the eight-arm maze, the total time to enter all eight arms decreased over five days from 192 to 73 s in li-saline rats while it remained constant in li-pilo rats (171-230 s). In li-saline rats, the number of arms visited and the number of errors per session decreased over five days but remained unchanged in li-pilo rats. The total time, total number of arms visited per session and total number of errors per day were significantly higher in li-pilo than in li-saline rats. In the object recognition task, the two groups spent a higher median time sniffing the new object, reflecting a comparable novelty preference. Neuronal loss reached 47-90% in hilus, hippocampal CA1 area, basolateral and medial amygdala, piriform and entorhinal cortex. These data confirm that in epileptic li-pilo rats, neuronal loss is extended in regions involved in memory such as hippocampus and entorhinal cortex which reflects the major impairments in spatial memory and the lack of strategy acquisition in the eight arm-maze also reported in rats with a shorter history of epilepsy. Likewise, the extended lesions in amygdala which mediates anxiety reflect the increase in the entries in open arms in the elevated plus-maze that are usually avoided by control rodents. In both tests, the animals were quite hyperactive reflecting a lack of goal-oriented activity. However, the performance in the object recognition task was similar in both groups which confirms previous data reporting that memory for objects is left relatively intact after hippocampal damage and appears to be spared even after a 5 months period of SRS. (Supported by INSERM grant U 398)