Dexamethasone alleviates motion sickness in rats in part by enhancing the endocannabinoid system

Eur J Pharmacol. 2014 Mar 15;727:99-105. doi: 10.1016/j.ejphar.2014.01.047. Epub 2014 Feb 4.

Abstract

Low-dose dexamethasone has been widely used for the prevention of nausea and vomiting after chemotherapy and surgical procedures and to treat motion sickness due to its minimal adverse effects, but the mechanisms underlying its anti-motion sickness effects are poorly understood. Previous studies have demonstrated that the endocannabinoid system is suppressed by motion sickness but stimulated by dexamethasone. The aim of the present study was to determine whether dexamethasone has an anti-motion sickness effect in rats and to elucidate the mechanism of this action. We used HPLC-MS/MS to measure the plasma concentrations of anandamide and 2-arachidonoylglycerol+1-arachidonoylglycerol, and we employed real-time quantitative PCR (qRT-PCR) and/or Western blot analysis to assay the expression of N-acylphosphatidyl-ethanolamine hydrolyzing phospholipase D, sn-1-selective diacylglycerol lipase, fatty acid hydrolase, monoacylglycerol lipase and endocannabinoid CB1 receptor in the dorsal vagal complex and stomach of rats exposed to a motion sickness protocol. The results showed that dexamethasone lowered the motion sickness index and restored the levels of endogenous cannabinoids and the expression of the endocannabinoid CB1 receptor, which declined after the induction of motion sickness, in the dorsal vagal complex and stomach.

Keywords: 2-AG; AEA; Glucocorticoid; Nausea and vomiting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiemetics / pharmacology*
  • Arachidonic Acids / blood
  • Dexamethasone / pharmacology*
  • Disease Models, Animal
  • Endocannabinoids / blood*
  • Glycerides / blood
  • Male
  • Motion Sickness / blood
  • Motion Sickness / physiopathology
  • Motion Sickness / prevention & control*
  • Polyunsaturated Alkamides / blood
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Severity of Illness Index
  • Signal Transduction / drug effects
  • Stomach / innervation*
  • Vagus Nerve / drug effects*
  • Vagus Nerve / metabolism
  • Vagus Nerve / physiopathology

Substances

  • 1-arachidonylglycerol
  • Antiemetics
  • Arachidonic Acids
  • Cnr1 protein, rat
  • Endocannabinoids
  • Glycerides
  • Polyunsaturated Alkamides
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Dexamethasone
  • glyceryl 2-arachidonate
  • anandamide