Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy

Background: The treatment of chronic pain presents a considerable difficulty, particularly due to opioid dependence, which is marked by tolerance and withdrawal symptoms. Opioids primarily target mu (μ) opioid receptors, providing pain relief while also leading to various side effects. This research...

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Main Authors: Tahereh Eteraf-Oskouei, Phd, Adel Mahmoudi Gharehbaba, Phd, Solmaz Asnaashari, Phd, Zahra Fazli, Phd, Bohloul Habibi Asl, Phd
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Current Therapeutic Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0011393X25000086
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author Tahereh Eteraf-Oskouei, Phd
Adel Mahmoudi Gharehbaba, Phd
Solmaz Asnaashari, Phd
Zahra Fazli, Phd
Bohloul Habibi Asl, Phd
author_facet Tahereh Eteraf-Oskouei, Phd
Adel Mahmoudi Gharehbaba, Phd
Solmaz Asnaashari, Phd
Zahra Fazli, Phd
Bohloul Habibi Asl, Phd
author_sort Tahereh Eteraf-Oskouei, Phd
collection DOAJ
description Background: The treatment of chronic pain presents a considerable difficulty, particularly due to opioid dependence, which is marked by tolerance and withdrawal symptoms. Opioids primarily target mu (μ) opioid receptors, providing pain relief while also leading to various side effects. This research aimed to examine the effectiveness of cetirizine and green tea hydroalcoholic extract (EXT) in altering morphine tolerance and improving analgesic effects. Methods: Adult male mice were divided into nine groups. In order to investigate the analgesic tolerance, animals received morphine on 14 consecutive days. Cetirizine (5, 10, 20 mg/kg, i.p.) and EXT (50, 100, 200 mg/kg, i.p.) were given before a test dose of morphine (9 mg/kg, i.p.). The analgesic effects were evaluated by the hot plate test. Results: Cetirizine with doses of 5, 10, 20 mg/kg, and 10 mg/kg showed a significant effect in reducing morphine tolerance 30 min (P < 0.0001) and 45 to 60 min (P < 0.0001) after test dose of morphine (9 mg/kg, i.p.) respectively. While the injection of different doses of the extract did not show any effect on tolerance to morphine. In the combined injection of these two drugs, there was no reduction in tolerance to morphine. Conclusions: Cetirizine but not EXT reversed morphine tolerance. Furthermore, the co-administration of cetirizine and EXT did not yield any significant benefits compared to the individual treatments.
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spelling doaj-art-ed4ca9d976a74c71ad6df2d20aee2dbb2025-08-20T02:35:44ZengElsevierCurrent Therapeutic Research0011-393X2025-01-0110210078310.1016/j.curtheres.2025.100783Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract EfficacyTahereh Eteraf-Oskouei, Phd0Adel Mahmoudi Gharehbaba, Phd1Solmaz Asnaashari, Phd2Zahra Fazli, Phd3Bohloul Habibi Asl, Phd4Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, IranBiotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Address correspondence to: Bohloul Habibi Asl, Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 51664, Iran.Background: The treatment of chronic pain presents a considerable difficulty, particularly due to opioid dependence, which is marked by tolerance and withdrawal symptoms. Opioids primarily target mu (μ) opioid receptors, providing pain relief while also leading to various side effects. This research aimed to examine the effectiveness of cetirizine and green tea hydroalcoholic extract (EXT) in altering morphine tolerance and improving analgesic effects. Methods: Adult male mice were divided into nine groups. In order to investigate the analgesic tolerance, animals received morphine on 14 consecutive days. Cetirizine (5, 10, 20 mg/kg, i.p.) and EXT (50, 100, 200 mg/kg, i.p.) were given before a test dose of morphine (9 mg/kg, i.p.). The analgesic effects were evaluated by the hot plate test. Results: Cetirizine with doses of 5, 10, 20 mg/kg, and 10 mg/kg showed a significant effect in reducing morphine tolerance 30 min (P < 0.0001) and 45 to 60 min (P < 0.0001) after test dose of morphine (9 mg/kg, i.p.) respectively. While the injection of different doses of the extract did not show any effect on tolerance to morphine. In the combined injection of these two drugs, there was no reduction in tolerance to morphine. Conclusions: Cetirizine but not EXT reversed morphine tolerance. Furthermore, the co-administration of cetirizine and EXT did not yield any significant benefits compared to the individual treatments.http://www.sciencedirect.com/science/article/pii/S0011393X25000086CetirizineGreen teaMorphineP-glycoproteinTolerance
spellingShingle Tahereh Eteraf-Oskouei, Phd
Adel Mahmoudi Gharehbaba, Phd
Solmaz Asnaashari, Phd
Zahra Fazli, Phd
Bohloul Habibi Asl, Phd
Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy
Current Therapeutic Research
Cetirizine
Green tea
Morphine
P-glycoprotein
Tolerance
title Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy
title_full Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy
title_fullStr Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy
title_full_unstemmed Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy
title_short Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy
title_sort reversing morphine induced tolerance insights into cetirizine and green tea extract efficacy
topic Cetirizine
Green tea
Morphine
P-glycoprotein
Tolerance
url http://www.sciencedirect.com/science/article/pii/S0011393X25000086
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