Clonidine attenuates conditioned aversion produced by naloxone-precipitated opiate withdrawal

Eur J Pharmacol. 1994 Mar 11;254(1-2):59-63. doi: 10.1016/0014-2999(94)90370-0.


Clonidine, an alpha 2-adrenoreceptor agonist, is used to alleviate withdrawal severity during detoxification from chronic opiate use. The effectiveness of clonidine has been challenged because it attenuates some, but not all, withdrawal signs in humans and animals. Because somatic assessments may not reflect opiate withdrawal aversion, this study used a one-trial place conditioning procedure. Naloxone was paired with the most preferred side and the amount of time spent on this side and on the vehicle-paired side was measured after training. This procedure led to a dose-related decrease in the time spent on the naloxone-paired side in morphine-exposed rats, but not in non-morphine-exposed rats. This conditioned place aversion shown by morphine-exposed rats was significantly attenuated by clonidine. These results suggest that in addition to clonidine's ability to lessen some somatic signs of opiate withdrawal, it also attenuates the aversive aspects of this state.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Avoidance Learning / drug effects*
  • Clonidine / pharmacology*
  • Dose-Response Relationship, Drug
  • Male
  • Morphine / pharmacology
  • Morphine Dependence / psychology*
  • Naloxone / antagonists & inhibitors*
  • Naloxone / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Substance Withdrawal Syndrome / psychology*


  • Naloxone
  • Morphine
  • Clonidine