Open AccessClonidine Attenuates Naloxone‐Induced Opioid‐Withdrawal Syndrome in Cholestatic Mice *
Author(s) -
Dehpour Ahmad Reza,
Samini Morteza,
Arad Mohammad Amin,
Namiranian Khodadad
Publication year - 2001
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1111/j.1600-0773.2001.890303.x
Subject(s) - clonidine , cholestasis , (+) naloxone , yohimbine , endocrinology , medicine , endogenous opioid , agonist , opioid antagonist , antagonist , opioid , opioid receptor , receptor
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 α 2 ‐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 α 2 ‐adrenoceptor antagonist, 15 min. before clonidine blocked this ameliorative effect of clonidine. The results of this study support the evidence for involvement of the α 2 ‐adrenoceptors in the withdrawal syndrome of cholestasis in a mouse model.