Citation

Vetreno RP, Crews FT. Neuroscience 2012; 226: 475-488.

Affiliation

The Bowles Center for Alcohol Studies, Department of Psychiatry, The University of North Carolina at Chapel Hill Chapel Hill, NC 27599 USA. Electronic address: rvetreno@email.unc.edu.

Copyright

(Copyright © 2012, International Brain Research Organization, Publisher Elsevier Publishing)

DOI

10.1016/j.neuroscience.2012.08.046

PMID

22986167

Abstract

Adolescence is a critical developmental stage of life during which the prefrontal cortex (PFC) matures, and binge drinking and alcohol abuse are common. Recent studies have found that ethanol increases neuroinflammation via upregulated high-mobility group box 1 (HMGB1) signaling through Toll-like receptors (TLRs). HMGB1/TLR 'danger signaling' induces multiple brain innate immune genes that could alter brain function. To determine whether adolescent binge drinking persistently increases innate immune gene expression in the PFC, rats (P25 to P55) were exposed to adolescent intermittent ethanol (AIE [5.0 g/kg, i.g., 2-day on/2-day off schedule]). Spatial and reversal learning was assessed in early adulthood (P64 to P75), and HMGB1/TLR danger signaling assessed using immunohistochemistry (i.e., + immunoreactivity [+IR]) for protein content and Real Time (RT)-PCR for mRNA in adulthood (P80). Immunohistochemistry and RT-PCR revealed that adult rats exposed to AIE had increased frontal cortical HMGB1, TLR4, and TLR3 expression in adulthood. Adolescent intermittent ethanol treatment did not alter adult spatial learning on the Barnes maze, but did cause reversal learning deficits and increased perseverative behavior. Barnes maze deficits correlated with the expression of danger signal receptors in the PFC. Taken together, these findings provide evidence that adolescent binge drinking leads to long-term activation of innate immune danger signaling in the adult PFC that correlates with adult neurocognitive dysfunction.

Language: en