Original Article

Acta Pharmacologica Sinica (2007) 28, 473–483; doi:10.1111/j.1745-7254.2007.00526.x

Neuropharmacology

Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys

This work was supported in part by grants from the Intramural Research Program of National Institute on Drug Abuse, NIH, USA and the 985 talent program of Peking University (No 985–2–046–121 and 985–2–027–39 to Lin Lu), the National Basic Research Program of China (No 20003CB 515400), and the National Natural Science Foundation of China (No 30570576 and 30670713 to Lin Lu).

Su-qing Chen2,5, Hai-feng Zhai2,5, Yan-ying Cui2,5, Jie Shi3, Bernard Le foll4 and Lin Lu2,4

  1. 2Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, Beijing 100083, China
  2. 3Department of Clinical Pharmacology, National Institute on Drug Dependence, Peking University, Beijing 100083, China
  3. 4Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA

Correspondence: Prof Lin Lu, Fax: 86-10-6203-2624. E-mail: linlu@bjmu.edu.cn

5These authors contributed equally to this work.

Received 19 September 2006; Accepted 8 November 2006.

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Abstract

Aim:

 

Clonidine is an alpha2 adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus monkeys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse.

Methods:

 

Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic) dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine.

Results:

 

Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized responses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previously treated with clonidine.

Conclusion:

 

Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may reduce subsequent effects of drugs of abuse after prolonged abstinence.

Keywords:

cocaine, withdrawal, drug challenge, cross-sensitization, recurrence, monkeys

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