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chronic intermittent ethanol; alcohol-use disorders; brain regional volumes; prefrontal cortex; hippocampal neurogenesis; basal forebrain; cell-death;orbitofrontal cortex; cognitive impairment; cholinergic neurons


Previous research has found that adolescent ethanol (EtOH) exposure alters drug seeking behaviors, cognition and neuroplasticity. Using male Sprague Dawley rats, differences in spatial working memory, non-spatial discrimination learning and behavioral flexibility were explored as a function of age at the onset (mid-adolescent vs. adult) of chronic EtOH exposure (CET). Concentrations of mature brain-derived neurotrophic factor (mBDNF) and betanerve growth factor (beta-NGF) in the prefrontal cortex and hippocampus were also assessed at different time-points: during CET, following acute abstinence (48-hrs), and after protracted abstinence (6-8 wks). Our results revealed that an adolescent onset of CET leads to increased EtOH consumption that persisted into adulthood. In both adult and adolescent onset CET groups, there were significant long-term reductions in prefrontal cortical mBDNF and beta-NGF levels. However, only adult onset CET rats displayed decreased hippocampal BDNF levels. Spatial memory, assessed by spontaneous alternation and delayed alternation, was not significantly affected by CET as a function of age of drinking onset, but higher blood-EtOH levels were correlated with lower spontaneous alternation scores. Regardless of the age of onset, EtOH exposed rats were impaired on non-spatial discrimination learning and displayed inflexible behavioral patterns upon reversal learning. Our results indicate that adolescent EtOH exposure changes long-term consumption patterns producing behavioral and neural dysfunctions that persist across the lifespan.

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Fernandez, G. M., Stewart, W. N., & Savage, L. M. (2016). Chronic Drinking During Adolescence Predisposes the Adult Rat for Continued Heavy Drinking: Neurotrophin and Behavioral Adaptation after Long-Term, Continuous Ethanol Exposure. PloS one, 11(3), e0149987.

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