title: Adolescent binge drinking alters adult brain neurotransmitter gene expression, behavior, brain regional volumes, and neurochemistry in mice.
abstract: BACKGROUND
  Binge drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol-use disorders.
  
  
  METHODS
  To determine whether adolescent ethanol (AE) binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5 g/kg/d, i.g., postnatal days P28 to P37) and assessed during adulthood (P60 to P88). An array of neurotransmitter-specific genes, behavioral tests (i.e., reversal learning, prepulse inhibition, and open field), and postmortem brain structure using magnetic resonance imaging (MRI) and immunohistochemistry, were employed to assess persistent alterations in adult brain.
  
  
  RESULTS
  At P38, 24 hours after AE binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38 to P88) resulted in decreased neurotransmitter mRNA, e.g., an average decrease of 56%. Following AE treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by AE treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following AE. Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons.
  
  
  CONCLUSIONS
  Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal forebrain acetylcholine neurons. Loss of cholinergic neurons and forebrain structure could underlie adult reversal learning deficits following adolescent binge drinking.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Leon G
authors.initials: LG
authors.lastname: Coleman
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Joohwi
authors.initials: J
authors.lastname: Lee
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.forename: Fulton T
authors.initials: FT
authors.lastname: Crews
mesh_terms: D000375:Aging; D000428:Alcohol Drinking; D019973:Alcohol-Related Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology / Q000506:poisoning*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000235:genetics; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology / Q000506:poisoning*; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009424:Nervous System Physiological Phenomena / Q000187:drug effects; D009474:Neurons; D018377:Neurotransmitter Agents / Q000235:genetics* / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000235:genetics / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D018377:Neurotransmitter Agents; D050638:Receptors, Dopamine D4; D000431:Ethanol; D002795:Choline O-Acetyltransferase; D004298:Dopamine