Summary:Purpose: In temporal lobe epilepsy (TLE), interictal behavioral disorders affect patients' quality of life. Therefore we studied long-term behavioral impairments in the lithiumpilocarpine (li-pilo) model of TLE.Methods: Eleven li-pilo adult rats exhibiting spontaneous recurrent seizures (SRSs) during 5 months were compared with 11 li-saline rats. Spatial working memory was tested in a radial arm maze (RAM), anxiety in an elevated plus-maze (EPM), and nonspatial working memory in an object-recognition paradigm. Neuronal loss was assessed on thionine brain sections after behavioral testing.Results: In the RAM, the time to complete each session and the number of errors per session decreased over a 5-day period in li-saline rats but remained constant and significantly higher in li-pilo rats. In the EPM, the number of entries in and time spent on open arms were significantly higher in li-pilo than li-saline rats. In the object-recognition task, the two groups exhibited a comparable novelty preference for the new object. Neuronal loss reached 47-90% in hilus, CA1, amygdala, and piriform and entorhinal cortex.Conclusions: In li-pilo rats having experienced SRS for 5 months, performance in the object-recognition task is spared, which suggests that object discrimination remains relatively intact despite extensive damage. Neuronal loss in regions mediating memory and anxiety, such as hippocampus, entorhinal cortex, and amygdala, may relate to impaired spatial orientation and decreased anxiety. Key Words: Temporal lobe epilepsyLithium-pilocarpine-Spatial memory-Object recognitionAnxiety-Neuronal damage.It is generally agreed that patients with temporal lobe epilepsy (TLE) are more prone to behavioral disorders and cognitive impairments than is the general population (1). These interictal impairments usually disrupt the patient's everyday life, often more than the seizures themselves (2,3). Furthermore, depression or anxiety often develops several years after epilepsy onset (2,4), and the control of the seizures with pharmacologic treatment does not always suppress these disorders (5). Among cognitive impairments, memory problems are frequently observed in patients with TLE. The most reliable observations are deficits in declarative memory (ability to acquire facts and events related to one's personal past, 6) and in the performance of visuospatial tasks (7-9). Moreover, long duration of refractory TLE seems to be associated with cognitive deterioration (10-12). Thus understanding the neural mechanism underlying these disturbances is an important Accepted November 28, 2004. Address correspondence and reprint requests to Dr. J. Detour at INSERM U666, Clinique Psychiatrique, Hôpitaux Universitaires, 1 place de l'hôpital, BP426, 67091 Strasbourg Cedex, France. E-mail: Julien.Detour@chru-strasbourg.fr issue in the management of TLE. In animal models of TLE, the molecular, lesional, and metabolic characteristics have been quite extensively studied. Conversely, the cognitive or behavioral validity of the models was less s...
