Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys.
OBJECTIVE
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.


CONCLUSIONS
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.
Chen
Su-qing
SQ
Departments of Neuropharmacology and Clinical Pharmacology, National Institute on Drug Dependence, Peking University, Beijing 100083, China.
Zhai
Hai-feng
HF
Cui
Yan-ying
YY
Shi
Jie
J
Le Foll
Bernard
B
Lu
Lin
L
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000627:therapeutic use*; D003042:Cocaine / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000009:adverse effects* / Q000494:pharmacology*; D009021:Morphine Dependence / Q000523:psychology; D009294:Narcotics / Q000009:adverse effects* / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology
D000316:Adrenergic alpha-Agonists; D009294:Narcotics; D009020:Morphine; D003042:Cocaine; D003000:Clonidine