title: Effects of protease-activated receptor 1 inhibition on anxiety and fear following status epilepticus.
abstract: Protease-activated receptor 1 (PAR1) is an important contributor to the pathogenesis of a variety of brain disorders associated with a risk of epilepsy development. Using the lithium-pilocarpine model of temporal lobe epilepsy (TLE), we recently showed that inhibition of this receptor during the first ten days after pilocarpine-induced status epilepticus (SE) results in substantial anti-epileptogenic and neuroprotective effects. As PAR1 is expressed in the central nervous system regions of importance for processing emotional reactions, including amygdala and hippocampus, and TLE is frequently associated with a chronic alteration of the functions of these regions, we tested the hypothesis that PAR1 inhibition could modulate emotionally driven behavioral responses of rats experiencing SE. We showed that SE induces a chronic decrease in the animals' anxiety-related behavior and an increase of locomotor activity. PAR1 inhibition after SE abolished the alteration of the anxiety level but does not affect the increase of locomotor activity in the open field and elevated plus maze tests. Moreover, while PAR1 inhibition produces an impairment of memory recall in the context fear conditioning paradigm in the control group, it substantially improves contextual and cued fear learning in rats experiencing SE. These data suggest that PAR1-dependent signaling is involved in the mechanisms underlying emotional disorders in epilepsy.
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Bogovyk
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: Oleksii
authors.initials: O
authors.lastname: Lunko
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: Mihail
authors.initials: M
authors.lastname: Fedoriuk
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Isaev
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
authors.forename: Oleg
authors.initials: O
authors.lastname: Krishtal
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Holmes
authors.affiliation: Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine; Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA. Electronic address: olena.isaeva@gmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Isaeva
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology*; D004833:Epilepsy, Temporal Lobe / Q000523:psychology; D005239:Fear / Q000187:drug effects / Q000523:psychology*; D008297:Male; D010862:Pilocarpine / Q000633:toxicity; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology*; D010975:Platelet Aggregation Inhibitors
chemical_list: C415424:N3-cyclopropyl-7-((4-(1-methylethyl)phenyl)methyl)-7H-pyrrolo(3, 2-f)quinazoline-1,3-diamine; D011758:Pyrroles; D011799:Quinazolines; D010862:Pilocarpine; D010975:Platelet Aggregation Inhibitors
keywords: Anxiety; Contextual and cued fear conditioning; Lithium-pilocarpine model; Memory; Protease-activated receptor 1; Temporal lobe epilepsy