Year: 2025
Type: dissertation
Abstract: Adolescence is a developmental period during the transition from childhood into adulthood that involves significant changes in neurobiology and behavioral. This time is often accompanied by increased risk-taking behavior, including binge drinking. Using a model of adolescent binge drinking, adolescent intermittent ethanol (AIE), test the hypothesis that without further alcohol consumption, the adult responses to acute alcohol challenge would be altered. The experiment used a 2 x 2 design, (AIE 5.0 g/kg; CONTROL on a 2-day-on/2-day-off schedule) during rat adolescence (PND 25 to 54) followed by a maturation period of 44-49 days without alcohol (PND 100-105) and an adult alcohol challenge (EtOH 4.0 g/kg; water). Assessments were immunoreactivity (+IR) in hippocampal dentate gyrus for a neuronal activity-regulated cytoskeletal (Arc) protein expressed in excited neurons, proinflammatory markers High mobility group box-1 (HMGB1) and cyclooxygenase-2 (COX-2), a marker of cell death cleaved caspase-3 (Casp3) and an enzymatic marker of DNA strand breaks, phosphorylated H2AX (gamma-H2AX). AIE increased HMGB1+IR and COX-2+IR, but did not change Arc+IR, Casp3+IR or gamma-H2AX+IR. Adult challenge with ethanol attenuated Arc+IR in alcohol naive rats, but no change in AIE treated rats. Adult challenge with ethanol reduced neuronal HMGB1+IR in alcohol naive rats, but not in AIE treated rats. Adult challenge with ethanol did not change COX-2+IR in alcohol naïve and AIE rats. Adult ethanol challenge did not affect Casp3 or gamma-H2AX in either AIE or controls. These results suggest that a history of AIE induces a tolerance to an adult ethanol challenge in Arc+IR and HMGB1+IR. Interestingly, AIE increased neuroimmune markers, HMGB1 and COX-2, however, the responses to an ethanol challenge differed. Since the granule cell layer of the dentate gyrus is neuronally dense, the expression of HMGB1 and Arc (a neuronal marker) suggest that AIE has altered adult neuronal responses to an adult acute binge drinking dose of ethanol consistent with long lasting changes in adult responses to acute ethanol following AIE.
DOI: 10.17615/xm98-h962
Author: Mosqueda, Aldrin
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6906603390
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