title: Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers.
abstract: The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30) received exposure to AIE (5g/kg, i.g.) or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR) test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.
authors.affiliation: Durham VA Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychology and Neuroscience, Duke University Medical Center Durham, Durham, North Carolina, 27705, United States of America.
authors.forename: H Scott
authors.initials: HS
authors.lastname: Swartzwelder
authors.affiliation: Durham VA Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, 27705, United States of America.
authors.forename: Shawn K
authors.initials: SK
authors.lastname: Acheson
authors.affiliation: Durham VA Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, 27705, United States of America.
authors.forename: Kelsey M
authors.initials: KM
authors.lastname: Miller
authors.affiliation: Durham VA Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, 27705, United States of America.
authors.forename: Hannah G
authors.initials: HG
authors.lastname: Sexton
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina, 27514, United States of America.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina, 27514, United States of America.
authors.forename: Fulton T
authors.initials: FT
authors.lastname: Crews
authors.affiliation: Durham VA Medical Center, Durham, North Carolina, 27705, United States of America; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, 27705, United States of America.
authors.forename: Mary-Louise
authors.initials: ML
authors.lastname: Risher
mesh_terms: D000818:Animals; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000187:drug effects*; D023421:Models, Animal; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000431:Ethanol