Influence of 5-HT3 receptor antagonists and the indirect 5-HT agonist, dexfenfluramine, on heroin self-administration in rats.
The purpose of the present study was to examine the effects of the 5-HT3 antagonists ondansetron and MDL72222, and the 5-HT releaser and reuptake inhibitor dexfenfluramine, on intravenous heroin self-administration by Wistar rats. Using separate squads of animals, two separate schedules of heroin reinforcement were used; a relatively low dose (0.03 mg/kg per infusion) made available under a FR5 schedule for 1 h each day, and a moderate heroin dose (0.1 mg/kg per infusion) available under a FR1 schedule for 2 h each day. Following the acquisition of stable levels of responding across days, both naloxone pretreatment (0.25 mg/kg SC) and halving the heroin infusion dose produced increases in operant responding for heroin at each concentration. Neither ondansetron (0.01-1 mg/kg SC) nor MDL72222 (0.1-3 mg/kg SC) pretreatment influenced heroin self-administration. Chronic treatment (5 day) of ondansetron (0.01-0.1 mg/kg) was similarly ineffective. However, dexfenfluramine (0.5-2.5 mg/kg IP) consistently reduced heroin self-administration at doses producing only modest decreases in food responding. These findings are in contrast to place conditioning studies, which show that 5-HT3 antagonists but not indirect 5-HT agonists block a morphine-induced place preference. Reasons for such discrepancies remain to be determined.
Preclinical Pharmacology and Experimental Psychology Program, Addiction Research Foundation, Toronto, Ontario, Canada.
G A
GA
Higgins
Y
Y
Wang
W A
WA
Corrigall
E M
EM
Sellers
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology*; D005502:Food; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology
D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; D005277:Fenfluramine; D009270:Naloxone; D017294:Ondansetron; D003932:Heroin; C042253:bemesetron