Year 2015, Volume 45, Issue 6, Pages 1380 - 1389 2015-12-04

Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences
Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences

ORUC ALLAHVERDİYEV [1] , ASLI ZENGİN TÜRKMEN [2] , ASİYE NURTEN [3] , İCLAL ŞEHİRLİ [4] , NURHAN ENGİNAR [5]

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Background/aim: Treating animals repeatedly with intermittent and increasing morphine doses has been suggested to allow some withdrawal during each dosing interval, which causes repeated stress. The present study aimed to test this hypothesis and assess sex-related differences in withdrawal signs and their suppression by clonidine. Materials and methods: Male and female rats and mice were administered with increasing doses of morphine twice daily at different dosing intervals. Rats were given clonidine in drinking water (5 μg/mL). Spontaneous and naloxone-precipitated withdrawal signs and novelty-induced grooming were evaluated. Results: Male rats and male and female rats displayed manifestations of morphine withdrawal at the end of 14-h and 24-h dosing intervals, respectively. Clonidine attenuated the severity of the withdrawal signs. Male but not female mice displayed withdrawal signs at the end of 12-h and 17-h dosing intervals. Female mice exhibited less pronounced naloxone-precipitated withdrawal syndrome. Grooming did not reflect a "stress-like state" in morphine-treated animals. Conclusion: These findings indicate intermittent morphine treatment-induced spontaneous withdrawal in rats and mice and sex-related differences in spontaneous and naloxone-precipitated withdrawal signs in mice. Since the treatment protocol closely parallels the drug use pattern in opioid addicts, further experiments are needed to clarify the stress associated with the treatment and the efficacy of sedatives.
Background/aim: Treating animals repeatedly with intermittent and increasing morphine doses has been suggested to allow some withdrawal during each dosing interval, which causes repeated stress. The present study aimed to test this hypothesis and assess sex-related differences in withdrawal signs and their suppression by clonidine. Materials and methods: Male and female rats and mice were administered with increasing doses of morphine twice daily at different dosing intervals. Rats were given clonidine in drinking water (5 μg/mL). Spontaneous and naloxone-precipitated withdrawal signs and novelty-induced grooming were evaluated. Results: Male rats and male and female rats displayed manifestations of morphine withdrawal at the end of 14-h and 24-h dosing intervals, respectively. Clonidine attenuated the severity of the withdrawal signs. Male but not female mice displayed withdrawal signs at the end of 12-h and 17-h dosing intervals. Female mice exhibited less pronounced naloxone-precipitated withdrawal syndrome. Grooming did not reflect a "stress-like state" in morphine-treated animals. Conclusion: These findings indicate intermittent morphine treatment-induced spontaneous withdrawal in rats and mice and sex-related differences in spontaneous and naloxone-precipitated withdrawal signs in mice. Since the treatment protocol closely parallels the drug use pattern in opioid addicts, further experiments are needed to clarify the stress associated with the treatment and the efficacy of sedatives.
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Primary Language tr
Journal Section Articles
Authors

Author: ORUC ALLAHVERDİYEV

Author: ASLI ZENGİN TÜRKMEN

Author: ASİYE NURTEN

Author: İCLAL ŞEHİRLİ

Author: NURHAN ENGİNAR

Dates

Publication Date: December 4, 2015

Bibtex @ { tbtkmedical149027, journal = {Turkish Journal of Medical Sciences}, issn = {1300-0144}, eissn = {1303-6165}, address = {TUBITAK}, year = {2015}, volume = {45}, pages = {1380 - 1389}, doi = {}, title = {Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences}, key = {cite}, author = {ALLAHVERDİYEV, ORUC and TÜRKMEN, ASLI ZENGİN and NURTEN, ASİYE and ŞEHİRLİ, İCLAL and ENGİNAR, NURHAN} }
APA ALLAHVERDİYEV, O , TÜRKMEN, A , NURTEN, A , ŞEHİRLİ, İ , ENGİNAR, N . (2015). Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences. Turkish Journal of Medical Sciences, 45 (6), 1380-1389. Retrieved from http://dergipark.org.tr/tbtkmedical/issue/12391/149027
MLA ALLAHVERDİYEV, O , TÜRKMEN, A , NURTEN, A , ŞEHİRLİ, İ , ENGİNAR, N . "Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences". Turkish Journal of Medical Sciences 45 (2015): 1380-1389 <http://dergipark.org.tr/tbtkmedical/issue/12391/149027>
Chicago ALLAHVERDİYEV, O , TÜRKMEN, A , NURTEN, A , ŞEHİRLİ, İ , ENGİNAR, N . "Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences". Turkish Journal of Medical Sciences 45 (2015): 1380-1389
RIS TY - JOUR T1 - Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences AU - ORUC ALLAHVERDİYEV , ASLI ZENGİN TÜRKMEN , ASİYE NURTEN , İCLAL ŞEHİRLİ , NURHAN ENGİNAR Y1 - 2015 PY - 2015 N1 - DO - T2 - Turkish Journal of Medical Sciences JF - Journal JO - JOR SP - 1380 EP - 1389 VL - 45 IS - 6 SN - 1300-0144-1303-6165 M3 - UR - Y2 - 2019 ER -
EndNote %0 Turkish Journal of Medical Sciences Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences %A ORUC ALLAHVERDİYEV , ASLI ZENGİN TÜRKMEN , ASİYE NURTEN , İCLAL ŞEHİRLİ , NURHAN ENGİNAR %T Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences %D 2015 %J Turkish Journal of Medical Sciences %P 1300-0144-1303-6165 %V 45 %N 6 %R %U
ISNAD ALLAHVERDİYEV, ORUC , TÜRKMEN, ASLI ZENGİN , NURTEN, ASİYE , ŞEHİRLİ, İCLAL , ENGİNAR, NURHAN . "Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences". Turkish Journal of Medical Sciences 45 / 6 (December 2015): 1380-1389.
AMA ALLAHVERDİYEV O , TÜRKMEN A , NURTEN A , ŞEHİRLİ İ , ENGİNAR N . Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences. Turkish Journal of Medical Sciences. 2015; 45(6): 1380-1389.
Vancouver ALLAHVERDİYEV O , TÜRKMEN A , NURTEN A , ŞEHİRLİ İ , ENGİNAR N . Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences. Turkish Journal of Medical Sciences. 2015; 45(6): 1389-1380.