Paper Information

Title:  EFFECTS OF ETHOSUXIMIDE ON MORPHINE TOLERANCE AND DEPENDENCE IN MICE
Type: POSTER
Author(s): IMEN SHAHIDI M.*,HOSSEINZADEH H.,ESHAGHIAN A.
 
 *DEPARTMENT OF PHARMACODYNAMY AND TOXICOLOGY, SCHOOL OF PHARMACY, MASHHAD UNIVERSITY OF MEDICAL SCIENCES
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Introduction: In this study, the effects of ethosuximide (an anticonvulsant with T-type calcium channel blocking activity) on the expression and development of morphine antinociceptive tolerance, and naloxone-precipitated abstinence syndrome in morphine dependent mice were investigated.
Methods: Mice were rendered tolerant and dependent on morphine by repeated administration of morphine. The tail-flick test was used to assess the nociceptive threshold, naloxone-induced jumping to assess the morphine dependence and open field to evaluate the locomotion.
Results: Repeated administration of ethosuximide (100, 200 and 400 mg/kg, 2time/day for 4 day) and also single administration of ethosuximide (100 mg/kg, simultaneously with last dose of morphine) reduced the development and expression of tolerance to the antinociceptive effect of morphine. Repeated administration of ethosuximide (100, 200 and 400 mg/kg, 3 time /day for 3 day) and also single administration of ethosuximide (100, 200 and 400 mg/kg, 30 min before the last dose of morphine) reduced the development and expression of naloxone-induced jumping in dependent mice that was comparable with clonidine (0.1 mg/kg) as positive control. Single (200 and 400 mg/kg) and repeated (only in 400 mg/ kg) administration of ethosuximide reduced the activity of animals in open field test. Ethosuximide in 200 and 400 mg/kg had direct antinociceptive effect that wasn't blocked by naloxone.
Conclusion: These results showed that ethosuximide, a relatively selective T-type calcium channel blocker has direct antinociceptive effect, prevents the development and expression of antinociceptive tolerance to morphine and suppress morphine withdrawal syndrome. 

 
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