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Antiepileptic drugs can induce both positive and adverse psychotropic effects, therefore evaluation of the behavioral effects of potential antiepileptic treatment early in the screening process is essential. Recently, we have shown that antagonist of protease-activated receptor 1 (PAR1), a major thrombin receptor in CNS, exhibits antiepileptogenic effect in the experimental model of temporal lobe epilepsy (TLE) reducing animal mortality, decreasing cell loss in hippocampal CA1 pyramidal region and probability of spontaneous recurrent seizures. PAR1 inhibition also improves contextual and cued fear learning and restores the control level of anxiety-related behavior in rats experiencing status epilepticus (SE). The aim of the present study was to determine the effect of PAR1 inhibition on the behavioral excitability of rats after SE. The experimental model of TLE was induced using intraperitoneal injections of lithium and pilocarpine. After that rats were treated with PAR1 inhibitor, SCH79797, for ten consecutive days. A battery of behavioral tests (approach-test, pick-up test, and touch-response test) was used for evaluation of behavioral hyperexcitability. We have found that SE induced different signs of the disturbance of behavior in response to sensory stimuli in pick-up test (average score of the test was 3.1 ± 0.6 in control animals and 5.2 ± 0.1 in animals with SE) and touch-response test (average score was 2.6 ± 0.6 and 5.7 ± 0.4 in rats without and with SE respectively). PAR1 inhibition did not affect the behavioral excitability of experimental rats. There was no significant difference between experimental groups in approach-test. Our results suggest the PAR1-independent development of disturbances of sensorimotor reactions during epileptogenesis in the current experimental model of TLE.

The protease-activated receptor 1 inhibition during epileptogenesis does not alter behavioral excitability in rats