title: Chronic intermittent ethanol exposure leads to alterations in brain-derived neurotrophic factor within the frontal cortex and impaired behavioral flexibility in both adolescent and adult rats.
abstract: Chronic intermittent exposure to ethanol (EtOH; CIE) that produces binge-like levels of intoxication has been associated with age-dependent deficits in cognitive functioning. Male Sprague-Dawley rats were exposed to CIE (5g/kg, 25% EtOH, 13 intragastric gavages) beginning at three ages: early adolescence (postnatal day [PD] 28), mid-adolescence (PD35) and adulthood (PD72). In experiment 1, rats were behaviorally tested following CIE. Spatial memory was not affected by CIE, but adult CIE rats were impaired at acquiring a non-spatial discrimination task and subsequent reversal tasks. Rats exposed to CIE during early or mid-adolescence were impaired on the first reversal, demonstrating transient impairment in behavioral flexibility. Blood EtOH concentrations negatively correlated with performance on reversal tasks. Experiment 2 examined changes in brain-derived neurotrophic factor (BDNF) levels within the frontal cortex (FC) and hippocampus (HPC) at four time points: during intoxication, 24 h after the final EtOH exposure (acute abstinence), 3 weeks following abstinence (recovery) and after behavioral testing. HPC BDNF levels were not affected by CIE at any time point. During intoxication, BDNF was suppressed in the FC, regardless of the age of exposure. However, during acute abstinence, reduced FC BDNF levels persisted in early adolescent CIE rats, whereas adult CIE rats displayed an increase in BDNF levels. Following recovery, neurotrophin levels in all CIE rats recovered. Our results indicate that intermittent binge-like EtOH exposure leads to acute disruptions in FC BDNF levels and long-lasting behavioral deficits. However, the type of cognitive impairment and its duration differ depending on the age of exposure.
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, United States.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Fernandez
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, United States.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Lew
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, United States.
authors.forename: Lindsey C
authors.initials: LC
authors.lastname: Vedder
authors.affiliation: Department of Psychology, Behavioral Neuroscience Program, Binghamton University, State University of New York, United States. Electronic address: lsavage@binghamton.edu.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Savage
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004193:Discrimination Learning / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000431:Ethanol
keywords: adult; chronic intermittent ethanol exposure; discrimination learning; early adolescence; mid-adolescence; reversal learning