Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST

Kristen E. Pleil, Christa Helms, Jon R. Sobus, James B. Daunais, Kathleen (Kathy) Grant, Thomas L. Kash

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Alterations in hypothalamic-pituitary-adrenal axis function contribute to many of the adverse behavioral effects of chronic voluntary alcohol drinking, including alcohol dependence and mood disorders; limbic brain structures such as the bed nucleus of the stria terminalis (BNST) may be key sites for these effects. Here, we measured circulating levels of several steroid hormones and performed whole-cell electrophysiological recordings from acutely prepared BNST slices of male rhesus monkeys allowed to self-administer alcohol for 12months or a control solution. Initial comparisons revealed that BNST neurons in alcohol-drinking monkeys had decreased membrane resistance, increased frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with no change in spontaneous excitatory postsynaptic currents (sEPSCs). We then used a combined variable cluster analysis and linear mixed model statistical approach to determine whether specific factors including stress and sex hormones, age and measures of alcohol consumption and intoxication are related to these BNST measures. Modeling results showed that specific measures of alcohol consumption and stress-related hormone levels predicted differences in membrane conductance in BNST neurons. Distinct groups of adrenal stress hormones were negatively associated with the frequency of sIPSCs and sEPSCs, and alcohol drinking measures and basal neuronal membrane properties were additional positive predictors of inhibitory, but not excitatory, PSCs. The amplitude of sEPSCs was highly positively correlated with age, independent of other variables. Together, these results suggest that chronic voluntary alcohol consumption strongly influences limbic function in non-human primates, potentially via interactions with or modulation by other physiological variables, including stress steroid hormones and age.

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

    Fingerprint

    Septal Nuclei
    Alcohol Drinking
    Primates
    Excitatory Postsynaptic Potentials
    Hormones
    Inhibitory Postsynaptic Potentials
    Membranes
    Steroids
    Neurons
    Alcoholic Intoxication
    Gonadal Steroid Hormones
    Patch-Clamp Techniques
    Macaca mulatta
    Mood Disorders
    Alcoholism
    Haplorhini
    Cluster Analysis
    Linear Models
    Alcohols
    Brain

    Keywords

    • Bed nucleus of the stria terminalis
    • Electrophysiology
    • Glucocorticoids
    • HPA axis
    • Rhesus monkey
    • Stress hormones
    • Synaptic transmission

    ASJC Scopus subject areas

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

    Cite this

    Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST. / Pleil, Kristen E.; Helms, Christa; Sobus, Jon R.; Daunais, James B.; Grant, Kathleen (Kathy); Kash, Thomas L.

    In: Addiction Biology, 2015.

    Research output: Contribution to journalArticle

    Pleil, Kristen E. ; Helms, Christa ; Sobus, Jon R. ; Daunais, James B. ; Grant, Kathleen (Kathy) ; Kash, Thomas L. / Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST. In: Addiction Biology. 2015.
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