Assessment of the multiple discriminative stimulus effects of ethanol using an ethanol-pentobarbital-water discrimination in rats

C. A. Bowen, G. J. Gatto, K. A. Grant

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    31 Scopus citations

    Abstract

    Previous drug discrimination studies have elucidated the importance of γ-aminobutyric acid(A) (GABA(A)), N-methyl-D-aspartate (NMDA) glutamate, and serotonin (5-HT) receptor systems in mediating the discriminative stimulus effects of ethanol. The present study used a three-choice operant drug discrimination procedure in an attempt to determine if salient GABAergic effects could be separated from other stimulus effects of 2.0 g/kg ethanol. Adult male Long-Evans rats (n=7) were trained to discriminate pentobarbital (10.0 mg/kg; intragastrically (i.g.)) from ethanol (2.0 g/kg; i.g.) from water (4.7 ml; i.g.) using food reinforcement, Stimulus substitution tests were conducted following the administration of allopregnanolone (1.0-17.0 mg/kg; intraperitoncally (i.p.)), diazepam (0.1-7.3 mg/kg; i.p.), midazolam (0.0056-17.0 mg/kg; i.p.), dizocilpine (0.01-0.56 mg/kg; i.p.), phencyclidine (1.0-5.6 mg/kg; i.p.), CGS 12066B (3-30 mg/kg; i.p.), RU 24969 (0.1-5.6 mg/kg; i.p.) and morphine (1 or 3.0 mg/kg; i.p.). Within the group, allopregnanolone and midazolam completely substituted (>80%), and diazepam partly substituted (67%) for the discriminative stimulus effects of pentobarbital. Dizocilpine and phencyclidine partly substituted (58 and 57%, respectively) for ethanol without substantial pentobarbital-appropriate responding. RU 24969, CGS 12066B and morphine did not result in complete substitution for either ethanol or pentobarbital, although RU 24969 resulted in partial (68%) pentobarbital substitution. The ability to train the present three-choice discrimination in rats indicates that the discriminative stimulus effects of 10.0 mg/kg pentobarbital were separable from those of 2.0 g/kg ethanol. The results suggest that the pharmacological effects of ethanol, which can control behavior, may seemingly be modified by training conditions (two-versus three-choice discrimination procedures), to the extent that a receptor system prominently linked to the behavioral activity of ethanol (i.e. GABA(A)) appears no longer to be involved in the interoceptive effects of the drug.

    Original languageEnglish (US)
    Pages (from-to)339-352
    Number of pages14
    JournalBehavioural Pharmacology
    Volume8
    Issue number4
    DOIs
    StatePublished - Oct 3 1997

    Keywords

    • 5HT agonists
    • Drug discrimination
    • Ethanol
    • GABA(A) positive modulators
    • Morphine
    • NMDA antagonists
    • Pentobarbital
    • Rat

    ASJC Scopus subject areas

    • Pharmacology
    • Psychiatry and Mental health

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