Abstracts

VOLTAGE-DEPENDENT CALCIUM CHANNEL AND NMDA RECEPTOR ANTAGONISTS AUGMENT ANTICONVULSANT EFFECTS OF LITHIUM CHLORIDE ON THE PENTYLENETETRAZOLE-INDUCED CLONIC SEIZURE IN MICE

Abstract number : 2.149
Submission category : 7. Antiepileptic Drugs
Year : 2010
Submission ID : 12743
Source : www.aesnet.org
Presentation date : 12/3/2010 12:00:00 AM
Published date : Dec 2, 2010, 06:00 AM

Authors :
Mehdi Ghasemi, H. Shafaroodi, A. Ghasemi and A. Dehpour

Rationale: There is some evidence that lithium could modulate seizure susceptibility in a variety of models of seizures in animals and epileptic patients. However, the underlying mechanisms of action of lithium have not been completely demonstrated. In this study using several calcium channel blockers (CCBs; nifedipine, verapamil, and diltiazem) and N-methyl-D-aspartate (NMDA) receptor antagonists (ketamine and MK-801) the involvement of calcium signaling in the effects of lithium chloride on pentylenetetrazole (PTZ)-induced seizure. Methods: PTZ-induced clonic seizure threshold was determined by inserting a 30 gauge butterfly needle into the tail vein of male Swiss mice (23-29 g) and the infusion of PTZ (0.5%) at a constant rate of 1 ml/min to unrestrained freely moving animals. Infusion was halted when forelimb clonus followed by full clonus of the body was observed. Minimal dose of PTZ (mg/kg of mice weight) needed to induce clonic seizure was considered as an index of seizure threshold. The one-way or two-way analysis of variance (ANOVA) followed by Newman-Keuls post hoc test was used to analyze the data. P < 0.05 was considered the significance level between the groups. Results: Acute lithium administration (5-100 mg/kg, i.p.) significantly (P < 0.01) increased the seizure threshold. CCBs (5-20 mg/kg, i.p.) and NMDA receptor antagonists (0.1-5 mg/kg ketamine and 0.01-0.1 mg/kg, i.p.) also exerted a dose-dependent anticonconvulsant effects on the PTZ-induced seizures. Non-effective doses of CCBs (nifedipine, verapamil, and diltiazem; 5 mg/kg, i.p.) when combined with non-effective dose of lithium (5 mg.kg, i.p.) exerted a significant anticonvulsant effects. Moreover, co-administration of non-effective doses of either MK-801 (0.05 mg/kg, i.p.) or ketamine (5 mg/kg, i.p.) with non-effective dose of lithium (5 mg/kg, i.p.) significantly increased the seizure threshold.
Antiepileptic Drugs