title: Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST.
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 12 months 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.
authors.affiliation: Bowles Center for Alcohol Studies & Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Pleil
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
authors.forename: Christa M
authors.initials: CM
authors.lastname: Helms
authors.affiliation: Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Sobus
authors.affiliation: Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Daunais
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Grant
authors.affiliation: Bowles Center for Alcohol Studies & Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. tkash@email.unc.edu.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Kash
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006728:Hormones / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012686:Septal Nuclei / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D006728:Hormones; D000431:Ethanol
keywords: HPA axis; bed nucleus of the stria terminalis; electrophysiology; glucocorticoids; rhesus monkey; stress hormones; synaptic transmission