Blockade of the discriminative stimulus effects of ethanol with 5-HT3 receptor antagonists

Kathleen A. Grant, James E. Barrett

    Research output: Contribution to journalArticle

    95 Scopus citations

    Abstract

    The ability of selective 5-HT3 receptor antagonists to block the discriminative stimulus effects of ethanol was investigated in pigeons trained with food reinforcement to discriminate ethanol (1.5 g/kg; IG) from water. The 5-HT3 receptor antagonists that are substituted tropines, ICS 205-930 (0.1-0.56 mg/kg) and MDL 72222 (3.0-17.0 mg/kg), blocked ethanol-appropriate responding, in a dose-dependent manner, suggesting that some of the discriminative stimulus effects of ethanol are mediated via the 5-HT3 receptor. The blockade the discriminative stimulus effects of ethanol occurred in the presence of approximately 25-40 mM blood ethanol levels. Furthermore, the ethanol dose-effect function was shifted to the right by increasing doses of MDL 72222, suggesting a surmountable antagonism of the discriminative stimulus effects of ethanol. However, the benzamide zacopride (0.56-1.7 mg/kg), which is also a 5-HT3 receptor antagonist, did not block the discriminative stimulus effects of ethanol. In addition, the dopaminergic antagonist haloperidol and the 5-HT2 receptor antagonist ketanserin also failed to block the ethanol discrimination. The results suggest that 5-HT3 mediated neurotransmission is an important component of ethanol's discriminative stimulus effects, but that the structural characteristics of the selective 5-HT3 receptor antagonists influence their ability to block this action of ethanol. Furthermore, these findings implicate a significant role of 5-HT3 activity in the behavioral effects of ethanol that may provide a pharmacological means for therapeutic intervention of alcohol abuse.

    Original languageEnglish (US)
    Pages (from-to)451-456
    Number of pages6
    JournalPsychopharmacology
    Volume104
    Issue number4
    DOIs
    StatePublished - Aug 1 1991

    Keywords

    • 5-HT
    • Drug -discrimination
    • Ethanol
    • Ethanol antagonist
    • Serotonin antagonists
    • Serotonin receptors

    ASJC Scopus subject areas

    • Pharmacology

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