Effects of ondansetron administration on opioid withdrawal syndrome observed in rats

Eur J Pharmacol. 1997 Dec 11;340(2-3):111-9. doi: 10.1016/s0014-2999(97)01349-6.


This study tested whether a 5-HT3 receptor antagonist could reverse the signs of precipitated opioid withdrawal. Rats were treated with either saline or morphine for 4 days. After the four days, half of the rats in each group received naloxone and half received saline. Each animal also received one of four doses of ondansetron (0, 1, 2 and 4 mg/kg i.p.). Administration of ondansetron to rats receiving naloxone after chronic morphine decreased the intensity of withdrawal signs such as increased defecation, jumping and wet-dog shakes, elevated the nociceptive threshold values which were decreased by precipitated withdrawal, but produced no change in urination, rectal temperature or salivation. The effects exhibited by ondansetron administration may be explained through interference of its 5-HT3 receptor antagonist activity with serotoninergic mechanisms involved in the regulation of these withdrawal symptoms. The use of this drug is thus suggested as a possible treatment of opioid withdrawal signs in heroin addicts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Body Temperature / drug effects
  • Defecation / drug effects
  • Male
  • Morphine / adverse effects*
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / adverse effects*
  • Ondansetron / pharmacology*
  • Pain Measurement / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Salivation / drug effects
  • Serotonin Antagonists / pharmacology*
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / psychology
  • Urination / drug effects


  • Narcotic Antagonists
  • Narcotics
  • Serotonin Antagonists
  • Naloxone
  • Ondansetron
  • Morphine