Abstracts

Rationale: Temporal lobe epilepsy is associated with high risk of psychiatric co-morbidities including anxiety and depression. In present study we focus on emotional alterations in animals with status epilepticus (SE)-induced epilepsy. We compared behavioral response of animals in standard tests and in a familiar environment of PhenoTypers to eliminate possible effects of altered adaptability of epileptic animals. Methods: LiCl/pilocarpine-induced SE was used to trigger epilepsy in adult male Wistar rats. Controls received saline instead of pilocarpine. SE was suppressed with paraldehyde (0.3 ml/kg ip) after 1.5 hr continual convulsions. The animals were submitted to a series of behavioral tests 10 days after status epilepticus and then again one month later. The tests were performed in the following order: (1) observation behavioral battery (approach-response, touch-response, finger-snap and pick-up tests) in order to discriminate the hyperexcitability of animals; (2) elevated plus maze test (EPM) to evaluate anxiety-related behavior; (3) PhenoTyper testing to detect behavior in a complex test situation. PhenoTypers (Noldus) were equipped with a shelter, water bottle, feeder, running wheel, and bedding to enable the animals monitoring in their home environment. The activity and movement displayed by rats was continuously measured (24h) and behavior during light and dark periods (12/12) were evaluated separately. Animals were continuously videomonitored for seizure detection. Results: All animals exposed to SE developed epilepsy and on average they exhibited 5.1 clonic seizures per week (min=1, max=23). Epileptic animals exhibited significant hyperexcitability in approach-response, touch-response and finger-snap tests in 10-day interval but not later. In the EPM test SE-animals spent significantly more time in open arms and by head dipping compared to controls in both intervals indicating no fear state behavior. In the PhenoTyper test, SE-animals were less active and spent more time in shelters during the light period than controls. SE-animals also exhibited significant difference in locomotor activity between light and dark periods and they spent longer time in the running wheel, suggesting higher activity compared to controls. Conclusions: Our results showed that SE elicited in adult rats lead to temporal behavioral manifestation related to hyperexcitability and long-term impairments in emotional domains. In complex environment of PhenoTypers SE-animals exhibited increased anxiety. Controversial behavior in the EPM can be interpreted as a behavioral disinhibition associated with novelty rather than a lower anxiety. Funding: This study was supported by European Regional Development Fund-Projects 'PharmaBrain' No. CZ.CZ.02.1.01/0.0/0.0/16_025/0007444, 19-11931S of the Czech Science Foundation, support for long-term conceptual development of research organization RVO: 67985823.