Adolescent intermittent ethanol exposure enhances ethanol activation of the nucleus accumbens while blunting the prefrontal cortex responses in adult rat.
The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on-2 days off; P25-P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). Using markers of neuronal activation c-Fos, EGR1, and phophorylated extracellar signal regulated kinase (pERK1/2), adult responses to a moderate and binge drinking ethanol challenge, e.g., 2 or 4 g/kg, were determined. Adult rats showed dose dependent increases in neuronal activation markers in multiple brain regions during ethanol challenge. Brain regional responses correlated are consistent with anatomical connections. AIE led to marked decreases in adult ethanol PFC (prefrontal cortex) and blunted responses in the amygdala. Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood.
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB 7178, Chapel Hill, NC 27599-7178, United States. Electronic address: wen_liu@med.unc.edu.
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Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB 7178, Chapel Hill, NC 27599-7178, United States. Electronic address: ftcrews@med.unc.edu.
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D000367:Age Factors; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D016760:Proto-Oncogene Proteins c-fos; D000431:Ethanol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
adolescence; alcohol; development; frontal cortex; networks