Voluntary ethanol consumption reduces GABAergic neuroactive steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) in the amygdala of the cynomolgus monkey

Matthew C. Beattie, Antoniette M. Maldonado-Devincci, Patrizia Porcu, Todd K. O'Buckley, James B. Daunais, Kathleen (Kathy) Grant, A. Leslie Morrow

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    Abstract

    Neuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) enhance the gamma-aminobutyric acid (GABA)-ergic effects of ethanol and modulate excessive drinking in rodents. Moreover, chronic ethanol consumption reduces 3α,5α-THP levels in human plasma, rat hippocampus and mouse limbic regions. We explored the relationship between 3α,5α-THP levels in limbic brain areas and voluntary ethanol consumption in the cynomolgus monkey following daily self-administration of ethanol for 12months and further examined the relationship to hypothalamic-pituitary-adrenal (HPA) axis function prior to ethanol exposure. Monkeys were subjected to scheduled induction of ethanol consumption followed by free access to ethanol or water for 22h/day over 12months. Immunohistochemistry was performed using an anti-3α,5α-THP antibody. Prolonged voluntary drinking resulted in individual differences in ethanol consumption that ranged from 1.2 to 4.2g/kg/day over 12months. Prolonged ethanol consumption reduced cellular 3α,5α-THP immunoreactivity by 13±2 percent (P

    Original languageEnglish (US)
    JournalAddiction Biology
    DOIs
    StateAccepted/In press - 2015

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    Keywords

    • Allopregnanolone
    • Amygdala
    • Chronic ethanol

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Psychiatry and Mental health
    • Pharmacology

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