Effects of Ionotropic Glutamate Receptor Blockers on Pentylenetetrazole-Induced Seizures in Krushinskii–Molodkina Rats

Abstract

Krushinskii–Molodkina (KM) rats have a genetic predisposition to increased audiogenic convulsive readiness and respond to sound signals with clonic-tonic convulsive seizures reminiscent of epileptic attacks in humans. The aims of the present work were to compare the neurological manifestations of the convulsant pentylenetetrazol (corazol) in Wistar and KM rats, i.e., to identify the contribution of genetically caused audiogenic convulsive readiness, and to assess the abilities of the NMDA receptor blockers memantine and 1-phenylcyclohexylamine (IEM-1921) to prevent the actions of pentylenetetrazol in KM rats. Convulsive reactions to administration of pentylenetetrazol were significantly stronger in KM rats than in Wistar rats, and deaths in KM rats were 2.1 times more frequent. Both blockers demonstrated the ability to reduce convulsive reactions to administration of pentylenetetrazol; the prophylactic action of IEM-1921 was more marked. IEM-1921 decreased the mean intensity of convulsive seizures by 2 points on a 5-point scale, while the total duration of generalized seizures decreased 41-fold. IEM-1921 completely prevented deaths among the animals, while memantine produce no more than a tendency to a decrease in lethality (68% in controls, 50% after administration of memantine). The results obtained here provide evidence that NMDA glutamate receptors play an important role in the molecular mechanisms of convulsive syndromes of different etiologies.