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

TitleEffects of chronic alcohol consumption on neuronal function in the non-human primate BNST
Publication TypeJournal Article
Year of Publication2016
AuthorsPleil KE, Helms CM, Sobus JR, Daunais JB, Grant KA, Kash TL
JournalAddict Biol
Volume21
Issue6
Pagination1151-1167
Date Published2016 Nov
ISSN1369-1600
KeywordsAlcohol Drinking, Animals, Central Nervous System Depressants, Ethanol, Excitatory Postsynaptic Potentials, Hormones, Hypothalamo-Hypophyseal System, Macaca mulatta, Male, Neurons, Pituitary-Adrenal System, Septal Nuclei, Synaptic Transmission
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.

DOI10.1111/adb.12289
Alternate JournalAddict Biol
PubMed ID26223349
PubMed Central IDPMC4732920
Grant ListU01 AA013510 / AA / NIAAA NIH HHS / United States
P51 OD011092 / OD / NIH HHS / United States
U01 AA020911 / AA / NIAAA NIH HHS / United States
F32 AA021043 / AA / NIAAA NIH HHS / United States
P60 AA011605 / AA / NIAAA NIH HHS / United States
P51 RR000163 / RR / NCRR NIH HHS / United States
U24 AA025475 / AA / NIAAA NIH HHS / United States
R24 AA019431 / AA / NIAAA NIH HHS / United States
K99 AA023559 / AA / NIAAA NIH HHS / United States
R21 AA023599 / AA / NIAAA NIH HHS / United States
R01 AA019454 / AA / NIAAA NIH HHS / United States