Paper Information

Title: 

EFFECTS OF CHRONIC ADMINISTRATION OF NICOTINE ON THE DEVELOPMENT OF MORPHINE TOLERANCE AND DEPENDENCE IN MALE MICE

Type: POSTER
Author(s): ALIZADEH A.M.*,HAGHPARAST A.,NADERI N.,KHANI A.,MOTAMEDI F.
 
 *NEUROSCIENCE RESEARCH CENTER, SHAHEED BEHESHTI MEDICAL UNIVERSITY, TEHRAN, 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:  2007Volume 18
 
 
Abstract: 

Introduction: Morphine is a widely used medication in pain management, but arising tolerance and dependency restricts its clinical use. Nicotine is widespread among smokers. So, investigating the interaction between nicotinic and opioid receptors is of great interest to both basic mechanistic view and clinical view. We studied effects of nicotine on the development of tolerance and dependency in morphine-treated mice.
Methods: Eighty NMRI male albino mice were rendered dependent on morphine by Marshall and Grahame-Smith method. Morphine sulfate was injected intraperitoneally (ip) three times daily on the following dosage schedule. The first three doses were 50, 50 and 75 mg/kg, respectively. Each of the doses was then increased by 25 mg/kg/day for maximum of three days. We used repeated administration of nicotine (0.001, 0.01, 0.1, 1, 2 mg/kg; ip) 15 min prior to each morphine injection along with control groups. Tail Flick latency before and after 50 mg/kg morphine injection in the fourth day was used as an index for development of tolerance. Likewise, number of jumping in 30-min period after naloxone administration (5 mg/kg; ip), 2 h post-injection of morphine in the fourth day was used as an index for dependency.
Results: Our findings showed that nicotine doses at 2, 1, and 0.1 mg/kg significantly reversed the development of tolerance. Dose of nicotine at 0.1 mg/kg was the most effective dose in dependency decrease.
Conclusion: The results indicate that repeated administration of nicotine reverses the development of morphine tolerance and dependency. Also, dose-response curve of nicotine vs. decrease in development of morphine dependency interestingly does not follow a non-linear manner and makes U-shape curve.

 
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