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

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.

• Authors: Tomohisa Mori, Sachiko Komiya, Jumpei Ohya, Naoki Uzawa, Koichi Sugiyama, Yusuke Saitoh, Masahiro Shibasaki, Tsutomu Suzuki
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 740 Pg. 160-7 (Oct 05 2014) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 25034809 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

• Animals
• Diarrhea (chemically induced, 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)