Involvement of 5-HT2 receptors in the expression of withdrawal diarrhea in morphine-dependent mice

Eur J Pharmacol. 2014 Oct 5:740:160-7. doi: 10.1016/j.ejphar.2014.07.009. Epub 2014 Jul 14.

Abstract

The withdrawal syndrome after the cessation of μ-opioid receptor agonists remains an obstacle in the clinical treatment of pain. We recently showed that peripheral opioid receptors play a significant role in the withdrawal signs in morphine-dependent mice. Therefore, the present study was designed to investigate the underlying mechanism of morphine-induced withdrawal symptoms, especially the peripheral oriented body-weight loss that accompanied diarrhea, in mice. Withdrawal signs were precipitated by the injection of naloxone 1 day after the slow-release emulsion administration of morphine. Withdrawal body-weight loss and diarrhea precipitated by naloxone in morphine-dependent mice were significantly suppressed by ritanserin (a 5-HT2 receptor antagonist), olanzapine (5-HT2/D2 receptor antagonist) and fullerene (a free radical scavenger), whereas neither ondansetron (a 5-HT3 receptor antagonist) nor atropine (a muscarine receptor antagonist) significantly suppressed naloxone-precipitated diarrhea. 5-HT3-receptors (but not 5-HT2-receptors) are known to play a significant role in 5-HT-induced diarrhea. Therefore, we also examined the effects of ritanserin and fullerene on 5-HT-induced diarrhea in morphine-dependent mice. Ritaserin significantly suppressed 5-HT-induced diarrhea in morphine-dependent mice, but not saline-treated mice. These results suggest that peripheral 5-HT2-receptor function could be altered in morphine-dependent mice, and the blockade of 5-HT2 receptor or free radical scavengers may be useful for the treatment of opioid-withdrawal diarrhea.

Keywords: 5-HT; Diarrhea; Morphine; Withdrawal signs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diarrhea / chemically induced
  • Diarrhea / metabolism*
  • Free Radical Scavengers / pharmacology
  • Fullerenes / pharmacology
  • Male
  • Mice, Inbred ICR
  • Morphine Dependence / metabolism*
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Receptors, Serotonin, 5-HT2 / metabolism*
  • Serotonin / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Substance Withdrawal Syndrome / metabolism*

Substances

  • Free Radical Scavengers
  • Fullerenes
  • Narcotic Antagonists
  • Receptors, Serotonin, 5-HT2
  • Serotonin Receptor Agonists
  • Serotonin
  • Naloxone