, Volume 114, Issue 4, pp 611–619 | Cite as

Influence of 5-HT3 receptor antagonists and the indirect 5-HT agonist, dexfenfluramine, on heroin self-administration in rats

  • Guy A. Higgins
  • Yephat Wang
  • William A. Corrigall
  • Edward M. Sellers
Original Investigations


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.

Key words

Heroin self-administration Rat 5-HT 2-HT3 receptor antagonists Ondansetron MDL72222 Indirect 5-HT agonist Dexfenfluramine Opioid reinforcement 


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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Guy A. Higgins
    • 1
    • 2
  • Yephat Wang
    • 1
    • 2
  • William A. Corrigall
    • 1
    • 2
  • Edward M. Sellers
    • 1
    • 2
  1. 1.Preclinical Pharmacology and Experimental Psychology Program, Addiction Research FoundationToronto
  2. 2.Departments of Pharmacology, Physiology and MedicineUniversity of TorontoTorontoCanada

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