Tropisetron attenuates naloxone-induced place aversion in single-dose morphine-treated rats: role of alpha7 nicotinic receptors

Eur J Pharmacol. 2009 May 1;609(1-3):74-7. doi: 10.1016/j.ejphar.2008.12.051. Epub 2009 Jan 17.

Abstract

We have previously reported that acute dependence can occur when naloxone is administered 24 h after even a single dose of morphine, and that nicotine attenuates this naloxone-precipitated withdrawal syndrome. In the present study, we studied the effect of tropisetron, an alpha7 nicotinic receptor agonist and 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist, on place aversion induced by naloxone in morphine-treated rats. Place aversion was significantly attenuated by pre-administered tropisetron (1.0 and 2.0 mg/kg, i. p.) in a dose-dependent manner, however tropisetron alone had no effect in a place-conditioning paradigm. This attenuation was completely antagonized by mecamylamine (1.0 mg/kg, s.c.), which is a central nicotinic receptor antagonist, but not by ondansetron (0.3 and 1.0 mg/kg, s.c.), a 5-HT(3) receptor antagonist. Furthermore, methyllycaconitine (1.0 and 2.0 mg/kg, s.c.), an alpha7 nicotinic acetylcholine receptor antagonist, but not dihydroxy-beta-erithroidine (1.0 and 2.0 mg/kg, s.c.), an alpha4beta2 nicotinic acetylcholine receptor antagonist, also antagonized the inhibitory effect of tropisetron. These findings suggest that tropisetron attenuates place aversion induced by naloxone in single-dose morphine-treated rats via alpha7 nicotinic receptors.

MeSH terms

  • Aconitine / analogs & derivatives
  • Aconitine / pharmacology
  • Animals
  • Conditioning, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Indoles / pharmacology*
  • Male
  • Mecamylamine / pharmacology
  • Morphine / pharmacology*
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / pharmacology*
  • Nicotinic Agonists / pharmacology
  • Nicotinic Antagonists / pharmacology
  • Ondansetron / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / metabolism*
  • Serotonin Antagonists / pharmacology
  • Tropisetron

Substances

  • Indoles
  • Narcotic Antagonists
  • Narcotics
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Serotonin Antagonists
  • methyllycaconitine
  • Naloxone
  • Ondansetron
  • Mecamylamine
  • Tropisetron
  • Morphine
  • Aconitine