Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 609, Issue 1-3, Pages 74-77Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.12.051
Keywords
Tropisetron; Place aversion; alpha 7 nicotinic receptor; 5-HT3 receptor
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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 alpha 7 nicotinic receptor agonist and 5-hydroxytryptamine 3 (5-HT3) 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-HT3 receptor antagonist. Furthermore, methyllycaconitine (1.0 and 2.0 mg/kg, s.c.), an alpha 7 nicotinic acetylcholine receptor antagonists but not dihydroxy-beta-erithroidine (1.0 and 2.0 mg/kg, s.c.), an alpha 4 beta 2 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 alpha 7 nicotinic receptors. (C) 2009 Elsevier B.V. All rights reserved.
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