PHARMACOLOGICAL BLOCKADE OF PROTEASE-ACTIVATED RECEPTORS 1 NORMALIZES BEHAVIORAL HYPEREXCITABILITY OF RATS IN THE LATENT STAGE OF THE EXPERIMENTAL MODEL OF TEMPORAL LOBE EPILEPSY
M. Semenikhina, R. Bogovik, M. Fedoryuk, О. Lunko, A Savotchenko, E. Isaeva
Bohomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz65.03.007
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Abstract
Temporal lobe epilepsy (TLE) leads to variety of neuropsychological
comorbidities, which may have severe impact on
social and emotional well-being and significantly reduce the
overall quality of life. In the present study, we demonstrate
the effect of blocking protease-activated receptor 1 (PAR1),
the main thrombin receptor in the central nervous system, on
hyperexcitability in the early stages of epilepsy formation. We
showed that inhibition of PAR1 leads to the normalization of
behavioral hyperexcitability of rats in the latent stage of temporal
lobe epilepsy in the lithium-pilocarpine model of status
epilepticus (SE) (in the pick-up test which is considered as the
most sensitive among tests used in the work: 2.4 ± 0.3 points
compared to 3.5 ± 0.58 points for the group after SE). The
obtained results correlate with previous studies of the effect
of PAR1 inhibition on animal behavior using pharmacological
approach and in animals with PAR1 knockout, and provide a
further evidence of the role PAR1 in the modulation of affective
behavior in TLE.
Keywords:
protease-activated receptors 1; lithium-pilocarpine model; status epilepticus; emotional excitability.
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