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Received: 2011-01-23

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Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.12 P.1016-1023


Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice

Author(s):  Reza Karami, Mahmoud Hosseini, Fatimeh Khodabandehloo, Leila Khatami, Zahra Taiarani

Affiliation(s):  Neuroscience Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran, Pharmacological Research Center of Medicinal Plants, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Corresponding email(s):   Hosseinim@mums.ac.ir

Key Words:  L-arginine, Ovariectomized mice, Morphine, Tolerance

Reza Karami, Mahmoud Hosseini, Fatimeh Khodabandehloo, Leila Khatami, Zahra Taiarani. Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice[J]. Journal of Zhejiang University Science B, 2011, 12(12): 1016-1023.

@article{title="Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice",
author="Reza Karami, Mahmoud Hosseini, Fatimeh Khodabandehloo, Leila Khatami, Zahra Taiarani",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice
%A Reza Karami
%A Mahmoud Hosseini
%A Fatimeh Khodabandehloo
%A Leila Khatami
%A Zahra Taiarani
%J Journal of Zhejiang University SCIENCE B
%V 12
%N 12
%P 1016-1023
%@ 1673-1581
%D 2011
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1100029

T1 - Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice
A1 - Reza Karami
A1 - Mahmoud Hosseini
A1 - Fatimeh Khodabandehloo
A1 - Leila Khatami
A1 - Zahra Taiarani
J0 - Journal of Zhejiang University Science B
VL - 12
IS - 12
SP - 1016
EP - 1023
%@ 1673-1581
Y1 - 2011
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1100029

Objective: The roles of gonadal hormones and nitric oxide (NO) on the analgesic effects of morphine, tolerance to morphine, and their interactions have been widely investigated. In the present study, the effect of l-arginine (an NO precursor) on morphine tolerance in sham and ovariectomized (OVX) female mice was investigated. Methods: Forty mice were divided into sham and OVX groups. On the first day, a hot plate test ((55±0.2) °C; cut-off 30 s) was carried out as a base record 15 min before injection of morphine (10 mg/kg, subcutaneously (s.c.)) and was repeated every 15 min after injection. The sham group was then divided into two subgroups: sham-tolerance-l-arginine (Sham-Tol-LA) and sham-tolerance-saline (Sham-Tol-Sal) which received either l-arginine 50 mg/kg (intraperitoneally (i.p.)) or saline 10 ml/kg (i.p.), respectively, three times in a day for three consecutive days. morphine tolerance was induced in animals by injecting 30 mg/kg morphine (s.c.) three times/day for three days. This treatment was also used for OVX subgroups. On the fifth day, the hot plate test was repeated. The analgesic effect of morphine was calculated as the maximal percent effect (MPE). The results were compared using repeated measure analysis of variance (ANOVA). Results: There was no significant difference in MPE between the OVX and sham groups. The MPEs in both the Sham-Tol-Sal and OVX-Tol-Sal groups were lower than those in both the sham and OVX groups (P<0.01). The MPE in the OVX-Tol-Sal group was greater than that in the Sham-Tol-Sal group (P<0.01). The MPE in the Sham-Tol-LA group was higher than that in the Sham-Tol-Sal group (P<0.01). However, there was no significant difference between the Sham-Tol-LA and sham groups or between the OVX-Tol-LA and OVX-Tol-Sal groups. Conclusions: The results of the present study showed that repeated administration of morphine causes tolerance to the analgesic effect of morphine. l-arginine could prevent tolerance to morphine but its effect was different in the presence of ovarian hormones.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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