Tropisetron attenuates naloxone-induced place aversion in single-dose morphine-treated rats: role of alpha7 nicotinic receptors.
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.
Department of Clinical Pharmacology and Pharmacy, Brain Science, Ehime University Graduate School of Medicine, Shitsukawa Toon, Ehime 791-0295, Japan.
Ranji
R
Cui
Katsuya
K
Suemaru
Bingjin
B
Li
Shuntaro
S
Kohnomi
Hiroaki
H
Araki
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D007211:Indoles; D009292:Narcotic Antagonists; D009294:Narcotics; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D012702:Serotonin Antagonists; C054634:methyllycaconitine; D009270:Naloxone; D017294:Ondansetron; D008464:Mecamylamine; D000077526:Tropisetron; D009020:Morphine; D000157:Aconitine