Clonidine attenuates naloxone-induced opioid-withdrawal syndrome in cholestatic mice.
Cholestasis is associated with elevated plasma level of endogenous opioid peptides. Naloxone-precipitated withdrawal syndrome has been described in a mouse model of acute cholestasis. Thus we aimed at determining whether central noradrenergic hyperactivity is involved in manifestation of naloxone-precipitated withdrawal syndrome in mice with obstructive cholestasis. Acute cholestasis was induced by bile duct resection in mice and physical dependence was observed by precipitating a withdrawal syndrome with naloxone (2 mg/kg, intraperitoneally) 5 days after induction of cholestasis. Administration of clonidine (0.1 mg/kg, intraperitoneally), an alpha2-adrenoceptor agonist, 15 min. before naloxone injection significantly alleviates withdrawal severity in cholestatic mice. However, pretreatment of animals with yohimbine (3 mg/kg, intraperitoneally), an alpha2-adrenoceptor antagonist, 15 min. before clonidine blocked this ameliorative effect of clonidine. The results of this study support the evidence for involvement of the alpha2-adrenoceptors in the withdrawal syndrome of cholestasis in a mouse model.
Dehpour
A R
AR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Dehpour@yahoo.com
Samini
M
M
Arad
M A
MA
Namiranian
K
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002779:Cholestasis / Q000139:chemically induced / Q000150:complications*; D003000:Clonidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000097:blood; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D015016:Yohimbine; D009270:Naloxone; D003000:Clonidine