Effects of pentylenetetrazol-induced kindling of seizures on rat emotional behavior and brain monoaminergic systems

Koncz

Acta Medica Marisiensis

et al. 2017

Objective: This study evaluated the anticonvulsant action of lacosamide (LCS), a novel drug that was recently approved for the treatment of partial or secondarily generalized seizures, using an animal model of generalized epilepsy induced by repetitive pentylenetetrazole (PTZ) administration in rats. The main goal was to evaluate the behavioral pattern of lacosamide action by classifying seizures according to a modified Racine-scale. Furthermore, the reproducibility of the win-PTZ kindling model of epilepsy, a recently described variant of the standard PTZ-kindling model, was also assessed. Methods: Adult male Wistar rats (n=16) were divided into two groups and underwent the win-PTZkindling protocol in two independent trials. After finishing the kindling procedure, all animals, which presented stage 5 seizures were tested for the anticonvulsant action of lacosamide at three different doses (3, 10, and 30 mg/kg). Results: The maximal severity of seizures decreased and the latency to stage 3-5 seizures increased when the animals were treated with lacosamide at a single dose of 10 mg/kg compared to saline pretreatment (p < 0.05), both parameter reflecting an anticonvulsant action of the drug. Unfortunately, the number of stage 3-5 seizures also increased, but not significantly. The win-PTZ kindling model showed an adequate reproducibility between different trials, however, the number of fully kindled rats was lower than previously reported. Conclusions: Lacosamide showed a convincing anticonvulsant action in the win-PTZ kindling model of epilepsy by preventing the generalization of seizures. The win-PTZ kindling model was proved to be useful for studying epileptogenesis and the anticonvulsant action of drugs.

Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ-Kindled Rats

Koncz

Acta Medica Marisiensis

et al. 2017

“…For example, the study that used pentylenetetrazol for evoking rats seizures (16), proposed that this may be due to the side effects of this drug. This can be further explained by the decrease in serotoninergic neurotransmission in the hippocampus and prefrontal cortex, which stands for the major regulatory stations, regarding the exploratory behavior.…”

Section: Discussionmentioning

confidence: 99%

Exploratory behavior alteration as an epileptic comorbidity in elevated plus maze test

Ademovič¹,

Lekovic²,

Knežević³

et al. 2017

Med podmladak

Introduction: Epileptic seizure consists of preictal, ictal and postictal period. Postictal period is characterized by a variety of psychiatric phenomenon of which the most frequent ones are anxiety and depressive disorder. Anxiety in rodents can be assessed by measuring the exploratory behavior. Lindane evokes generalized tonic-clonic epileptic seizures in rats, when applied intraperitoneally, due to its lypophilic characteristics. Aim: The aim of this study was to assess exploratory behavior linked with anxiety level in the elevated plus maze test (EPM) upon generalized seizures, induced by lindane in male rats. Material and methods: The experiment was conducted on Wistar albino male rats that were randomly divided into: control group (DMSO, 0.5 ml/kg) and experimental group (lindane, 8 mg/kg) (n=8, each). After the drug injection, the assessment of the seizure intensity lasted for 30 minutes. Descriptive rating scale was used to describe the seizure severity. Subsequently, the EPM testing took place immediately after evoking the seizure (Test 1), after 1h (Test 2) and after 24h (Test 3). Time spent in open areas and number of transitions was further analyzed. Results: Experimental group of animals spent less time in open areas of EPM, when compared to controls in Test 1 and Test 2. The same holds true for the number of transitions to the open area, i.e. lindane-treated animals tend to stay in enclosed parts of the maze in Test1, Test 2. Finally, in Test 3 there was no significant difference between the groups, in any parameter of interest. Conclusion: Lindane-induced generalized epileptic seizures are accompanied by reduced exploratory behavior in the elevated plus maze test, up to 24h after the seizure ended. This finding can be a basis for the further translational research of anxiety as epileptic comorbidity in this experimental model of epilepsy.

“…17 At final injection (named challenge dose, twelfth periods or day 24 th ), PTZ was injected at dose 75 mg/kg to the animals. The animals were followed for convulsion scores (0-5) during thirty minutes after PTZ injection.…”

Section: Ptz-induced (Kindling) Seizuresmentioning

confidence: 99%

Pentylenetetrazol-induced seizures strength in diabetic and normal serum glucose elevated male mice

2016

Background: Epilepsy is one of the most important neurological disorders, afflicting both genders during their lifetime. Metabolic disturbances, including hyperglycemia and hypoglycemia, are one of the main reasons of seizures in which frequently have been seen in diabetes mellitus. A large body of literature has investigated correlation between hyperglycemia, hypoglycemia and seizure. However, a definitive conclusion has not been taken, yet. Hence, we developed a rodent model of PTZ-induced seizure in order to investigate about relation between PTZ-induced seizures and glycemic changes, including diabetic and non-diabetic hyperglycemia and hypoglycemia.Methods: We chose 50 naive, adult male inbred mice of the Balb/c strain (aged 8–10 weeks, weighted 25-35 grams) and divided them into 5 groups, randomly (n=10 in each groups): 1. Control (received saline and citrate buffer). 2. Diabetic group (received STZ 140 mg/kg I.P). 3. Diabetic+Glibenclamide group (received STZ 140 mg/kg I.P and treated with Glibenclamide 1 mg/kg I.P daily). 4. Non-diabetic hyperglycemic group (received glucose "D-dextrose" 2 g/kg I.P 30 min before PTZ administration. 5. Hypoglycemic group (the animals were fasted one day other days during experimental period). Chemical kindling was induced by PTZ injection (35 mg/kg, I.P), every other days (11 periods that lasted 22 days). Results: Our data shown non-diabetic hyperglycemic mice that had elevated blood glucose levels, were more resistant to seizures compared to control group (p<0.05). Threshold and duration of the second phase of the seizures in non-diabetic hyperglycemic mice were increased (p<0.001). Moreover, threshold of the phase 5 was enhanced (p<0.001). Again, hypoglycemic mice had statistically significant decrease in threshold of phase 5 compared to control group (p<0.05).Conclusions: We found that acute non-diabetic hyperglycemia not only have had no aggravating effects on seizure susceptibility but also have shown anticonvulsive effects. As well, we found that hypoglycemia has decreased threshold of phase 5 in challenge dose, i.e. onset of the most severe phase of the seizures was accelerated.