The effect of clonidine on the naltrexone-induced withdrawal response in morphine-treated guinea-pigs.
Rapid opioid withdrawal induced by naltrexone is now used as a treatment for heroin addiction. The alpha2-adrenoceptor agonist, clonidine, is currently used in clinical practice to reduce opioid withdrawal in humans. However, few studies have been reported on its effectiveness for this purpose. Guinea-pigs were made dependent and tolerant to morphine using a 3-day chronic morphine regimen (total 410 mg kg(-1) morphine base), and injected with either clonidine (0.1 mg kg(-1), s.c.) or saline, 1 h before induction of withdrawal with naltrexone (15 mg kg(-1), s.c.). Withdrawal behaviours were measured for 90 min and animals were then euthanased and the brains removed. The presence of the immediate early gene protein product, c-Fos, was detected using immunohistochemical techniques. Clonidine reduced the number of head/body shakes, but had no effect on the total withdrawal behaviour score. In the CNS, clonidine increased the number of Fos-LI neurons in the central amygdala. In conclusion, the modest effect of clonidine in the present experiments suggests that the efficacy of clonidine in humans undergoing naltrexone-induced opioid withdrawal requires further investigation.
Jungnickel
Sebastian
S
Experimental Pharmacology Unit, School of Biomedical Sciences, University of Newcastle, NSW, Australia.
Chahl
Loris A
LA
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000627:therapeutic use*; D005260:Female; D016762:Genes, fos / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D009021:Morphine Dependence / Q000188:drug therapy*; D009270:Naloxone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*
D000316:Adrenergic alpha-Agonists; D009292:Narcotic Antagonists; D009270:Naloxone; D003000:Clonidine