5HT3 receptor antagonists block morphine- and nicotine- but not amphetamine-induced reward.
The effect of two potent and specific antagonists of 5HT3 receptors, ICS 205-930 and MDL 72222, on the reinforcing properties of amphetamine, morphine and nicotine was studied in rats. Drug-induced reinforcement was assessed by measuring drug-conditioned place preference. ICS 205-930 and MDL 72222 dose-dependently reduced the place preference induced by morphine (1.0 mg/kg SC). At doses of 0.030 mg/kg SC the two antagonists completely blocked morphine-induced place preference while doses of 0.015 mg/kg SC significantly reduced it. ICS 205-930 and MDL 72222 at doses of 0.030 mg/kg SC also prevented the place preference induced by nicotine (0.6 mg/kg SC). In contrast, ICS 205-930 and MDL 72222 up to doses of 0.030 mg/kg SC failed to modify the place preference elicited by amphetamine (1.0 mg/kg SC). The results indicate that 5HT3 receptors are specifically involved in the reinforcing properties of morphine and nicotine.
Carboni
E
E
Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Italy.
Acquas
E
E
Leone
P
P
Di Chiara
G
G
D000661:Amphetamine / Q000037:antagonists & inhibitors*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors*; D009538:Nicotine / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012201:Reward; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology; D000077526:Tropisetron
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D000077526:Tropisetron; D009538:Nicotine; D009020:Morphine; D000661:Amphetamine; C042253:bemesetron