Discriminative stimulus effects of ethanol in rats using a three-choice ethanol-midazolam-water discrimination

P. Porcu, K. A. Grant

    Research output: Contribution to journalArticle

    7 Scopus citations

    Abstract

    Three-choice discrimination procedures are used to characterize how similar the discriminative stimulus effects of two drugs are in relation to each other. This procedure has suggested similarities between ethanol and ligands that positively modulate the γ-aminobutyric acid type A (GABAA) receptor complex. As an extension to these studies, male Long-Evans rats were trained to discriminate midazolam (3.0 mg/kg, i.p.) from ethanol (1.0 g/kg, i.g.) from water (2.3 ml, i.g.) in a three-lever, food reinforced task. Substitution tests were conducted following administration of GABA A-positive modulators, noncompetitive N-methyl-D-aspartate (NMDA) antagonists, 5-HT1B agonists and isopropanol. Among the GABA A-positive modulators, diazepam was the only drug that completely substituted for midazolam; both pentobarbital and the neurosteroid allopregnanolone showed partial midazolam substitution. The NMDA antagonist dizocilpine substituted for ethanol, while phencyclidine showed no substitution for either ethanol or midazolam. The serotonin agonists tested also showed no substitution for either ethanol or midazolam. Isopropanol was the only other drug that completely substituted for ethanol. These data extend previous findings from an ethanol-pentobarbital-water discrimination and further define training conditions that result in a conditional basis for the ethanol discrimination where only those drugs with pharmacological heterogeneous effects similar to ethanol produce a full ethanol-like effect.

    Original languageEnglish (US)
    Pages (from-to)555-567
    Number of pages13
    JournalBehavioural Pharmacology
    Volume15
    Issue number8
    DOIs
    StatePublished - Dec 2004

    Keywords

    • 5-HT agonists
    • Alcohol
    • Drug discrimination
    • Ethanol
    • GABA-positive modulators
    • Midazolam
    • NMDA antagonists
    • Rat

    ASJC Scopus subject areas

    • Pharmacology
    • Psychiatry and Mental health

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