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Cited by 197Prenatal Substance Exposure EffectsSubstance Abuse Treatment and OutcomesNeurotransmitter Receptor Influence on Behavior

Adolescent Binge Drinking Alters Adult Brain Neurotransmitter Gene Expression, Behavior, Brain Regional Volumes, and Neurochemistry in Mice: ADULT BRAIN FOLLOWING ADOLESCENT BINGE

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Coleman Jr, Leon G., He, Jun, Lee, Joohwi, Styner, Martin, Crews, Fulton T.·2011·Alcoholism: Clinical and Experimental Research
DOI 10.1111/j.1530-0277.2010.01385.xPMC PMC3544413
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Abstract

BACKGROUND: Binge drinking is common in human adolescents. The adolescent brain is undergoing structural maturation and has a unique sensitivity to alcohol neurotoxicity. Therefore, adolescent binge ethanol may have long-term effects on the adult brain that alter brain structure and behaviors that are relevant to alcohol-use disorders. METHODS: To determine whether adolescent ethanol (AE) binge drinking alters the adult brain, male C57BL/6 mice were treated with either water or ethanol during adolescence (5 g/kg/d, i.g., postnatal days P28 to P37) and assessed during adulthood (P60 to P88). An array of neurotransmitter-specific genes, behavioral tests (i.e., reversal learning, prepulse inhibition, and open field), and postmortem brain structure using magnetic resonance imaging (MRI) and immunohistochemistry, were employed to assess persistent alterations in adult brain. RESULTS: At P38, 24 hours after AE binge, many neurotransmitter genes, particularly cholinergic and dopaminergic, were reduced by ethanol treatment. Interestingly, dopamine receptor type 4 mRNA was reduced and confirmed using immunohistochemistry. Normal control maturation (P38 to P88) resulted in decreased neurotransmitter mRNA, e.g., an average decrease of 56%. Following AE treatment, adults showed greater gene expression reductions than controls, averaging 73%. Adult spatial learning assessed in the Morris water maze was not changed by AE treatment, but reversal learning experiments revealed deficits. Assessment of adult brain region volumes using MRI indicated that the olfactory bulb and basal forebrain were smaller in adults following AE. Immunohistochemical analyses found reduced basal forebrain area and fewer basal forebrain cholinergic neurons. CONCLUSIONS: Adolescent binge ethanol treatment reduces adult neurotransmitter gene expression, particularly cholinergic genes, reduces basal forebrain and olfactory bulb volumes, and causes a reduction in the density of basal forebrain acetylcholine neurons. Loss of cholinergic neurons and forebrain structure could underlie adult reversal learning deficits following adolescent binge drinking.

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  • Rodent models suggest that alterations in FC morphology following adolescent exposure to alcohol may be persistent, as rats exposed to chronic intermittent alcohol during adolescence had a bilateral reduction in prefrontal cortex thickness and basal forebrain volume as adults.

    “Rodent models suggest that alterations in FC morphology following adolescent exposure to alcohol may be persistent, as rats exposed to chronic intermittent alcohol exposure during the adolescent period had a bilateral reduction in prefrontal cortex thickness and basal forebrain volume as adults (Coleman et al. 2011; Vetreno et al. 2017).”

    From The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse (2018) · cites this paper as Coleman et al. 2011

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  • Certain aspects of HC-dependent learning and memory, such as spatial learning and memory, were not impacted following adolescent alcohol exposure but were in adults.

    “Although there is evidence for persistent neurological and cognitive deficits in HC function, it is important to note that certain aspects of HC-dependent learning and memory, such as spatial learning and memory, were not impacted following adolescent exposure (Coleman et al. 2011; Vetreno and Crews 2012) but were in adults (Cippitelli et al. 2010).”

    From The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse (2018) · cites this paper as Coleman et al. 2011

  • Similar adult deficits in behavioral flexibility due to adolescent ethanol exposure have been observed using the Morris water maze and set shifting models.

    “Similar adult deficits in behavioral flexibility, due to adolescent ethanol exposure, have also been observed using the Morris water maze (Coleman et al. 2011) and set shifting models (Gass et al. 2014).”

    From The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse (2018) · cites this paper as Coleman et al. 2011

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Authors
Coleman Jr, L. G., He, J., Lee, J., Styner, M., & Crews, F. T.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Crews, Fulton T.
ORCID
Venue
Alcoholism: Clinical and Experimental Research
Publisher
Wiley
Published
2011-01-11
Volume
35
Issue
4
Pages
671-688
ISSN
0145-6008 (ISSN-L)
DOI
10.1111/j.1530-0277.2010.01385.x
PMC
PMC3544413
OpenAlex
W2167489219
Cited by
197
References
9
Citations by year
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FWCI
12.74
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1694 d)
Locations
  • Alcoholism Clinical and Experimental Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism (P50AA011605, U24AA020022, U01AA020023, AA011605, AA020023, AA018051, F30AA018051, AA06069, AA020022, U24AA020024, R37AA006069, R01AA006069, P60AA011605)
  • National Institute on Drug Abuse (P01DA022446)
  • National Institute of Neurological Disorders and Stroke (R42NS059095)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30-HD03110, P30HD003110)
  • Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
adolescent binge drinking, ethanol exposure, cholinergic neurons, dopaminergic neurons, dopamine D4 receptor, prepulse inhibition, olfactory bulb, basal forebrain, acetylcholine, alcohol neurotoxicity, alcohol use disorder risk, mouse model
MeSH terms
Aging, Alcohol Drinking, Ethanol, Animals, Brain, Central Nervous System Depressants, Choline O-Acetyltransferase, Dopamine, Male, Motor Activity, Nervous System Physiological Phenomena, Neurons, Gene Expression, Neurotransmitter Agents, Maze Learning, Alcohol-Related Disorders, Receptors, Dopamine D4, Mice

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