The effect of N-methyl-D-aspartate receptor antagonists on D,L-homocysteine thiolactone induced seizures in adult rats

Abstract

The aim of our study was to investigate the effects of ifenprodil and MK-801 on D,L-homocysteine thiolactone induced seizures in adult rats.Male Wistar rats were divided into following groups: 1. Saline-treated (C, n=10); 2. D,L-homocysteine thiolactone 8 mmol/kg, i.p. (H, n=7); 3. Ifenprodil 20 mg/kg i.p. (IF, n=8); 4. MK-801 0.5 mg/kg, i.p. (MK, n=8) and 5. Groups that received IF or MK 30 minutes prior to H (IFH, n=8 and MKH, n=8). Seizure behavior was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. Lethality in experimental group was recorded 90 min and 24 h upon D,L-homocysteine thiolactone administration.There were no behavioral signs of seizure activity in groups C, IF and MK.Pre-treatment with MK-801 (MKH) showed tendency to reduced incidence of convulsions, latency to the first seizure onset and the severity of seizure episodes, but statistical significance was not attained comparing to the H group. However, median number of seizure episodes was significantly decreased in MKH (p<0.05), comparing to the H group. On the other hand, ifenprodil (IFH) decreased the latency to the first seizure onset and increased the median number of seizure episodes (p<0.05). The majority of seizure episodes in IFH (72.1%, p<0.05) and MKH (73.1%, p<0.05) groups was grade 2 and significantly different comparing to the H (36.0%). Our findings suggest that MK-801 has a mild anticonvulsive effect on D,L-homocysteine thiolactone induced seizures in adult rats.

Homocysteine and homocysteine-related compounds: an overview of the roles in the pathology of the cardiovascular and nervous systems

“…Previously published study confirms this assertion (Marković et al 2011). Namely, administration of folic acid 30 minutes prior to DL-Hcy TLHC decreased the incidence of seizures and increased latency, as well as mean total spectral power density in EEG recording.…”

Homocysteine: Neurotoxicity and mechanisms of induced hyperexcitability

“…The majority of seizure episodes in the ifenprodil (72.1%) and MK-801 (73.1%) groups were significantly different compared to the D,L-homocysteine thiolactone treated group (36.0%). Our findings suggest that D,L-homocysteine thiolactone induces seizures through the stimulation of NMDA receptors in the central nervous system but other mechanisms (i.e., NO signalling) may also be involved (58).…”

Multidisciplinary approach to nitric oxide signaling: Focus on gastrointestinal and central nervous system

“…Recently, Stanojlović et al 59 showed that acute administration of HCT to adult rats significantly alters neuronal circuits, leading to epileptogenic activity in the EEG with characteristic spikes-and-wave discharges (SWD), and convulsive episodes (manifested through 5grade descriptive rating scale addapted by Stanojlović et al 59 ) in animal behavior. HCT-induced seizures are accepted as a suitable model of generalized epileptic seizures in which coexistence of convulsive and absence-like seizures were proven 60,61 . This is one of the advantages of this particular epilepsy model which allowed reliable investigations of variety seizure activity modifications, like paradoxical sleep deprivation 62 .…”