Paper Information

Title: 

EFFECT OF GABAPENTIN AND SODIUM SELENITE COADMINISTRATION ON THE DEVELOPMENT OF TOLERANCE TO MORPHINE ANALGESIA AND DEPENDENCE IN MICE

Type: POSTER
Author(s): CHARKHPOUR M.*,YAGHOUBIFARD S.,HASANZADEH KAMBIZ,HABIBIASL B.
 
 *SCHOOL OF PHARMACY, TABRIZ UNIVERSITY OF MEDICAL SCIENCES, TABRIZ, IRAN
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2009Volume 19
 
 
Abstract: 

Glutaminergic system is involved in the development of tolerance and dependence on analgesic effect of opioids. Recent studies have shown the inhibitory actions of gabapentin and sodium selenite on NMDA receptors. However, other reports show the analgesic effect of gabapentin. In this study, we evaluate individual effects of gabapentin and sodium selenite alone as well as co-administration of these drugs on the development of dependence on morphine. Experiments were performed on 18 groups (n=8) of Albino Swiss male mice weighing 25-30g. Animals received saline (10 ml/kg, i.p.), vehicle (saline, 10 ml/kg, i.p.) with morphine (50 mg/kg, i.p.), morphine with gabapentin (10, 20, 40 mg/kg, i.p.) or sodium selenite (1, 2, 4 mg/kg, i.p.), morphine with both of drugs (gabapentin 10 mg and sodium selenite 1 mg) for a period of four days. On the fifth day, a hot-plate test was done after administration of test dose of morphine (9 mg/kg, i.p.). In order to assay the effect of gabapentin and sodium selenite on morphine dependence, animals received morphine (50 mg/kg, s.c.) and saline or drugs for five days. Two hours after the last dose of morphine, naloxone (4 mg/kg, i.p.) was injected and withdrawal signs (jumping and standing on feet) were recorded for 30 minutes. The results showed that gabapentin (in all three doses) and sodium selenite (in two higher doses) decreased morphine tolerance (p<0.05) and coadministration of these drugs had an additive effect (p<0.05). In dependence studies, the administration of gabapentin and sodium selenite alone decreased withdrawal signs (in two higher doses- jumping: p<0.01, standing on feet: p<0.05) and gabapentin plus sodium selenite had an additive effect only on jumping (p<0.001). Our data indicate that glutaminergic system and additive effect of the related antagonists have an essential role on development of tolerance and dependence on morphine.

 
Keyword(s): MORPHINE, GABAPENTIN, SODIUM SELENITE, TOLERANCE, DEPENDENCE, WITHDRAWAL SYNDROME
 
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