عنوان مجله
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Basic and Clinical Neuroscience
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کلیدواژهها
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Isoniazid, Morphine,
Conditioned place preference,
Tolerance, Sensitization,
Reward
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چکیده
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481
July, August 2020, Volume 11, Number 4
Research Paper: Effects of Isoniazid on Tolerance and
Sensitization to the Rewarding Properties of Morphine:
A Conditioned Place Preference Procedure Investigation
in Mice
Amir Abbas Barzegari1* , Kamran Shahabi1
1. Department of Biology, Faculty of Basic Science, University of Maragheh, Maragheh, Iran.
* Corresponding Author:
Amir Abbas Barzegari, PhD.
Address: Department of Biology, Faculty of Basic Science, University of Maragheh, Maragheh, Iran.
Tel: +98 (41) 37278001
E-mail: barzegaridoctora@gmail.com
Introduction: The GABAergic system of the brain plays a key role in morphine tolerance and
sensitization. As isoniazid is a modulator of the GABAergic system, the present study aims to
understand whether isoniazid can influence the induction of tolerance and sensitization to the
rewarding effects of morphine.
Methods: The rewarding effects of morphine and isoniazid were assessed using a Conditioned
Place Preference (CPP) procedure in female mice. Tolerance to the rewarding effects of
morphine was induced with high-dose morphine (25 mg/kg, SC), twice a day, for four days.
Also, the sensitization was induced with an effective dose of morphine (5 mg/kg, SC), once a
day, for three days. During the induction of tolerance or sensitization, the different groups of
mice received saline or isoniazid (25, 50, and 75 mg/kg, IP) one hour before each morphine
injection.
Results: Morphine (0.5-10 mg/kg, SC) produced a significant CPP, but isoniazid (25, 50, and
75 mg/kg, IP) did not induce place preference or place aversion in mice. Although an effective
dose of morphine (5 mg/kg, SC) did not induce CPP in morphine tolerated mice, an ineffective
dose (0.5 mg/kg, SC) could produce a significant CPP in morphine-sensitized animals.
The administration of isoniazid before morphine (on the days of tolerance or sensitization
induction) inhibited the development of tolerance or sensitization to the rewarding effect of
morphine in the CPP parad
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