TY  - JOUR
TI  - Spontaneous withdrawal in intermittent morphine administration in rats and mice: effect of clonidine coadministration and sex-related differences
AB  - Background/aim: Treating animals repeatedly with intermittent and increasing morphine doses has been suggested to allow somewithdrawal 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 differentdosing intervals. Rats were given clonidine in drinking water (5 µg/mL). Spontaneous and naloxone-precipitated withdrawal signs andnovelty-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 dosingintervals, respectively. Clonidine attenuated the severity of the withdrawal signs. Male but not female mice displayed withdrawal signsat 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 parallelsthe drug use pattern in opioid addicts, further experiments are needed to clarify the stress associated with the treatment and the efficacyof sedatives.
AU  - ŞEHİRLİ, İclal
AU  - ZENGİN TÜRKMEN, Aslı
AU  - Enginar, Nurhan
AU  - NURTEN, Asiye
AU  - ALLAHVERDİYEV, Oruc
PY  - 2015
JO  - Turkish Journal of Medical Sciences
VL  - 45
IS  - 6
SN  - 1300-0144
SP  - 1380
EP  - 1389
DB  - TRDizin
UR  - http://search/yayin/detay/186573
ER  -