Paper Information

Title: 

MECHANISMS OF EFFECTS OF EXPERIMENTAL DIABETES ON DEVELOPMENT OF MORPHINE TOLERANCE IN RAT

Type: POSTER
Author(s): JOUHARCHI KH.*,JORJANI M.
 
 *DEP. OF PHARMACOLOGY, FACULTY OF MEDICINE, SHAHEED BEHESHTI MEDICAL UNIVERSITY, TEHRAN
 
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: Several neuroendocrine complications including diabetes change the morphine antinociception and the development of tolerance to this drug. Morphine antinociception was reduces significantly in morphine tolerant diabetic rats compared to non-diabetic animals. The exact mechanism of this effect is not known. Thus this study was performed to determine the role of nitric oxide (NO) on morphine tolerance in diabetic state.
Methods: Experimental diabetes was induced   by a single injection of alloxan (100 mg/kg, s.c.). Nociceptive responses were measured using hot-plate test. Administration of morphine sulfate (7 mg/kg, i.p., once/d for 5 consecutive days) developed tolerance in animals. Then, 24-hours urine was collected and the nitric oxide level was measured in both diabetic and non-diabetic morphine tolerated animals using spectrophotometric method with Griess reagent. For the conversion of nitrate to nitrite, vanadium chloride was used. L-arginine (100 mg/kg, i.p.) as a NO precursor and aminoguanidine (60 mg/kg, i.p.) as a selective iNOS inhibitor were used.
Results:  The results showed that experimental diabetes increased morphine analgesia. Conversely, degree of tolerance to morphine was diminished in diabetic state (P<0.001). The urinary nitrite content in diabetic morphine tolerated rats was higher than non-diabetic groups. L-arginine significantly increased the NO production in diabetic morphine tolerated animals, whereas aminoguanidine decreased it. Appropriately, L-arginine increased the latency time of reaction to noxious stimuli in diabetic compared to non-diabetic rats. L-arginine- treated animals also showed more tolerance to morphine analgesia. As expected, aminoguanidine deducted the level of morphine tolerance in diabetic animals.
Conclusion: It is suggested that NO has a modulatory role in the effects of diabetes on morphine analgesia and tolerance.

 
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