title: Adolescent, but not adult, binge ethanol exposure leads to persistent global reductions of choline acetyltransferase expressing neurons in brain.
abstract: During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55) treatment led to persistent, global reductions of choline acetyltransferase (ChAT) expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70) produced a reduction in ChAT+IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+IR in the basal forebrain following adolescent (P28-P48) and adult (P70-P90) binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity.
authors.affiliation: Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Vetreno
authors.affiliation: Center for Developmental and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, New York, 13902, United States of America.
authors.forename: Margaret
authors.initials: M
authors.lastname: Broadwater
authors.affiliation: Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Center for Developmental and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, New York, 13902, United States of America.
authors.forename: Linda P
authors.initials: LP
authors.lastname: Spear
authors.affiliation: Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States of America.
authors.forename: Fulton T
authors.initials: FT
authors.lastname: Crews
mesh_terms: D000293:Adolescent; D000328:Adult; D057229:Alcoholics; D000818:Animals; D000831:Animals, Newborn; D001344:Autopsy; D063425:Binge Drinking; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013997:Time Factors; D014886:Weaning; D055815:Young Adult
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D002795:Choline O-Acetyltransferase