TY - JOUR

T1 - The NMDA Receptor Channel Blockers Memantine and IEM-1921 Decrease the Duration of Status Epilepticus in Wistar and Krushinskii–Molodkina Rats in a Lithium-Pilocarpine Model

AU - Vataev, S. I.

AU - Zaitsev, A. V.

AU - Lukomskaya, N. Ya

AU - Magazanik, L. G.

N1 - Publisher Copyright: © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2020/3/1

Y1 - 2020/3/1

N2 - Chronic experiments on Wistar and Krushinskii–Molodkina rats, which have an inherited predisposition to audiogenic convulsions, addressed the effects of preliminary administration of memantine and IEM-1921 – NMDA glutamate receptor channel blockers – on brain electrical activity on development of status epilepticus (SE) induced by pilocarpine. Electrograms were recorded from the hippocampus, caudate nucleus, and the somatosensory, visual, and auditory areas of the cortex. The nature and sequence of changes in the phases of SE identifi ed from electrogram patterns were not altered by blockers. In addition, the latent period of the onset of epileptiform activity on the EEG after administration of pilocarpine to Wistar rats decreased almost two-fold (to 10–15 min) after administration of memantine (5 mg/kg) or IEM-1921 (5 mg/kg). In Krushinskii–Molodkina rats, the latent period of development of epileptiform activity was initially shorter (13 ± 2 min) and was not altered by use of blockers. The mean durations of SE after administration of memantine to Wistar and Krushinskii–Molodkina rats were 2 and 3 times, respectively, shorter than without blocker, while durations were reduced seven-fold by IEM-1921. NMDA receptor blockers also signifi cantly weakened behavioral motor convulsions, decreasing the intensity of convulsions from 8 to 4 points on the Pinel and Rovner [1978] scale. These data provide evidence that blockade of NMDA receptors did not prevent the typical development of pilocarpine-induced SE, though duration was signifi cantly reduced.

AB - Chronic experiments on Wistar and Krushinskii–Molodkina rats, which have an inherited predisposition to audiogenic convulsions, addressed the effects of preliminary administration of memantine and IEM-1921 – NMDA glutamate receptor channel blockers – on brain electrical activity on development of status epilepticus (SE) induced by pilocarpine. Electrograms were recorded from the hippocampus, caudate nucleus, and the somatosensory, visual, and auditory areas of the cortex. The nature and sequence of changes in the phases of SE identifi ed from electrogram patterns were not altered by blockers. In addition, the latent period of the onset of epileptiform activity on the EEG after administration of pilocarpine to Wistar rats decreased almost two-fold (to 10–15 min) after administration of memantine (5 mg/kg) or IEM-1921 (5 mg/kg). In Krushinskii–Molodkina rats, the latent period of development of epileptiform activity was initially shorter (13 ± 2 min) and was not altered by use of blockers. The mean durations of SE after administration of memantine to Wistar and Krushinskii–Molodkina rats were 2 and 3 times, respectively, shorter than without blocker, while durations were reduced seven-fold by IEM-1921. NMDA receptor blockers also signifi cantly weakened behavioral motor convulsions, decreasing the intensity of convulsions from 8 to 4 points on the Pinel and Rovner [1978] scale. These data provide evidence that blockade of NMDA receptors did not prevent the typical development of pilocarpine-induced SE, though duration was signifi cantly reduced.

KW - EEG

KW - IEM-1921

KW - Krushinskii–Molodkina rats

KW - lithium-pilocarpine model of epilepsy

KW - memantine

KW - NMDA receptors

KW - status epilepticus

UR - http://www.scopus.com/inward/record.url?scp=85079554649&partnerID=8YFLogxK

U2 - 10.1007/s11055-020-00909-y

DO - 10.1007/s11055-020-00909-y

M3 - Article

VL - 50

SP - 374

EP - 383

JO - Neuroscience and Behavioral Physiology

JF - Neuroscience and Behavioral Physiology

SN - 0097-0549

IS - 3

ER -