Nicotine self-administration and locomotor activity are not modified by the 5-HT3 antagonists ICS 205-930 and MDL 72222.
The subtype-selective serotonin 5-HT3 antagonists MDL 72222 and ICS 205-930 were tested for their ability to modify nicotine self-administration and locomotor activity in rats. In self-administration experiments, MDL 72222 produced no statistically significant changes over a dose range of 1 to 30 micrograms/kg, nor at the considerably higher dose of 1 mg/kg. MDL 72222 was similarly without effect in nicotine-produced locomotor activity, except at the 1 mg/kg dose, which reduced scores. In an initial test on nicotine self-administration, ICS 205-930 produced a small decrease in drug-taking behavior at 1 and 3 micrograms/kg which just reached statistical significance, but had no effects at higher doses. However, these low-dose effects could not be replicated. In addition, ICS 205-930 was without effect on nicotine locomotor activity, even at the two low doses that had reduced self-administration. We conclude that these 5-HT3 antagonists do not modulate nicotine reinforcement or behavioral arousal.
Corrigall
W A
WA
Addiction Research Foundation, University of Toronto, Ontario, Canada.
Coen
K M
KM
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012055:Reinforcement Schedule; D012646:Self Administration / Q000523:psychology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology*; D000077526:Tropisetron
D007211:Indoles; D012702:Serotonin Antagonists; D014326:Tropanes; D000077526:Tropisetron; D009538:Nicotine; C042253:bemesetron