Drug discrimination analysis of endogenous neuroactive steroids in rats

Nancy A. Ator, Kathleen A. Grant, Robert H. Purdy, Steven M. Paul, Roland R. Griffiths

    Research output: Contribution to journalArticle

    112 Scopus citations

    Abstract

    Rats were trained in a two-lever procedure to discriminate either pentobarbital (10 mg/kg), ethanol (1.5 g/kg), diazepam (1 mg/kg), or lorazepam (1 mg/kg) from the no-drug condition. Consistent with previous reports, rats in the pentobarbital, ethanol, and diazepam training conditions all showed complete dose-dependent generalization to pentobarbital under test conditions, but rats trained to discriminate lorazepam did not. Administration of the neuroactive steroids 3α, 21-dihydroxy-5α-pregnan-20-one (3α,5α-THDOC) and 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) also produced complete generalization in rats trained to discriminate pentobarbital, ethanol, and diazepam, but not in rats trained to discriminate lorazepam. These results further indicate the specificity of the lorazepam training condition and are consistent with neurochemical data indicating that these neuroactive steroids are similar to barbiturates in modulating γ-aminobutyric acid (GABA)A receptors. In the context of previous data, the results from the four training groups suggest that the discriminative-stimulus effects of the neuroactive steroids are sedative/anxiolytic in nature and probably mediated through a non-benzodiazepine GABAA site.

    Original languageEnglish (US)
    Pages (from-to)237-243
    Number of pages7
    JournalEuropean Journal of Pharmacology
    Volume241
    Issue number2-3
    DOIs
    StatePublished - Sep 14 1993

    Keywords

    • Behaviour
    • Benzodiazepines
    • Drug discrimination
    • Ethanol
    • Neuroactive steroids
    • Pentobarbital

    ASJC Scopus subject areas

    • Pharmacology

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