Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures

2016 ◽  
Vol 57 ◽  
pp. 95-104 ◽  
Author(s):  
Kathrin Töllner ◽  
Friederike Twele ◽  
Wolfgang Löscher
Keyword(s):  
Surrogate Model ◽  
Drug Testing ◽  
Seizure Threshold ◽  
Threshold Test

Effects of propofol and thiopentone on picrotoxin convulsive threshold in the rabbit

1995 ◽  
Vol 73 (6) ◽  
pp. 714-717 ◽  
Author(s):  
Zyheir Hasan ◽  
Said Khatib ◽  
Ayman Abu-Laban
Keyword(s):  
Intravenous Administration ◽  
Seizure Threshold ◽  
Intravenous Anesthetics ◽  
Threshold Test ◽  
Dose Dependent Increase ◽  
Convulsive Threshold ◽  
Dose Dependent ◽  
Higher Doses

The purpose of the present study was to examine the effect of intravenous administration of propofol and thiopentone on picrotoxin-induced seizures using the picrotoxin convulsive threshold test in the rabbit. Neither propofol nor thiopentone at a dose of 1.25 mg/kg had any significant effect on picrotoxin seizure threshold. However, at higher doses (2.5, 5, 10 mg/kg) both propofol and thiopentone produced a significant and dose-dependent increase in the picrotoxin convulsive threshold. These findings suggest that propofol is an effective anticonvulsant against picrotoxin-induced seizures in the rabbit.Key words: convulsions, intravenous anesthetics, picrotoxin, propofol, thiopentone.

scholarly journals The Effects and Mechanisms of Action of TC-G 1008, GPR39 Agonist, in Animal Models of Seizures and Epilepsy

2022 ◽  
Author(s):  
Urszula Doboszewska ◽  
Katarzyna Socala ◽  
Mateusz Pieróg ◽  
Dorota Nieoczym ◽  
Jan Sawicki ◽  
...  
Keyword(s):  
Serum Zinc ◽  
Mass Spectrometry Analysis ◽  
Emission Spectrometry ◽  
Seizure Threshold ◽  
Total Serum ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Threshold Test ◽  
Zebrafish Larvae ◽  
Ptz Kindling

Abstract Background and purpose: The G-protein coupled receptor 39 (GPR39) may be activated by zinc ions. Activation of GPR39 was suggested as a novel pharmacological strategy for treating seizures. Experimental approach: We utilized a specific agonist of GPR39, TC-G 1008, and the nonspecific agonist, zinc chloride and a variety of models of acute seizures or a chronic model of epilepsy which were induced in non-genetically modified mice, GPR39 knockout mice or in zebrafish larvae. We examined total serum zinc (by Inductively Coupled Plasma Optical Emission Spectrometry) as well as intracellular zinc ([Zn2+]I) (by Zinpyr-1 staining) concentrations and the expression of selected proteins (by Western blot) which are associated with GPR39 signaling in the hippocampus. Key results: Liquid chromatography tandem mass spectrometry analysis showed that TC-G 1008 is brain penetrant. TC-G 1008 decreased the seizure threshold in the maximal electroshock seizure (MES) threshold test, but it increased the seizure threshold in the 6-Hz induced seizure threshold test. The behavioral effects of TC-G 1008 and MES or 6-Hz seizure were accompanied by alterations in hippocampal [Zn2+]I. TC-G 1008 increased the mean duration of EEG discharges in response to pentylenetetrazole (PTZ) in zebrafish larvae and facilitated the development of PTZ kindling in mice. Using GPR39 knockout mouse line, generated by the CRISPR-Cas-9 method, we showed that GPR39 is a target for TC-G 1008 regarding PTZ-induced epileptogenesis. Conclusion and implications: Our in vivo data obtained using TC-G 1008 generally argue against GPR39 activation as a therapeutic strategy for alleviating seizures/epilepsy.

scholarly journals Salvinorin A Does Not Affect Seizure Threshold in Mice

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1204
Author(s):  
Katarzyna Socała ◽  
Urszula Doboszewska ◽  
Piotr Wlaź
Keyword(s):  
Opioid Receptor ◽  
Muscular Strength ◽  
Motor Coordination ◽  
Clonic Seizure ◽  
Seizure Threshold ◽  
Salvinorin A ◽  
Maximal Electroshock ◽  
Threshold Test ◽  
Opioid Receptor Agonist ◽  
Chimney Test

The κ-opioid receptor has recently gained attention as a new molecular target in the treatment of many psychiatric and neurological disorders including epilepsy. Salvinorin A is a potent plant-derived hallucinogen that acts as a highly selective κ-opioid receptor agonist. It has unique structure and pharmacological properties, but its influence on seizure susceptibility has not been studied so far. Therefore, the aim of the present study was to investigate the effect of salvinorin A on seizure thresholds in three acute seizure tests in mice. We also examined its effect on muscular strength and motor coordination. The obtained results showed that salvinorin A (0.1–10 mg/kg, i.p.) did not significantly affect the thresholds for the first myoclonic twitch, generalized clonic seizure, or forelimb tonus in the intravenous pentylenetetrazole seizure threshold test in mice. Likewise, it failed to affect the thresholds for tonic hindlimb extension and psychomotor seizures in the maximal electroshock- and 6 Hz-induced seizure threshold tests, respectively. Moreover, no changes in motor coordination (assessed in the chimney test) or muscular strength (assessed in the grip-strength test) were observed. This is a preliminary report only, and further studies are warranted to better characterize the effects of salvinorin A on seizure and epilepsy.

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