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Cited by 16Memory and Neural MechanismsPosttraumatic Stress Disorder ResearchNeurotransmitter Receptor Influence on Behavior

Adolescence alcohol exposure impairs fear extinction and alters medial prefrontal cortex plasticity

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Lawson, K., Scarlata, M.J., Cho, W.C., Mangan, C., Petersen, D., Thompson, H.M., Ehnstrom, S., Mousley, A.L. +2 more·2022·Neuropharmacology
DOI 10.1016/j.neuropharm.2022.109048PMC PMC9067297
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Abstract

After experiencing a traumatic event people often turn to alcohol to cope with symptoms. In those with post-traumatic stress disorder (PTSD) and a co-occurring alcohol use disorder (AUD), PTSD symptoms can worsen, suggesting that alcohol changes how traumatic memory is expressed. The objective of this series of experiments is to identify how alcohol drinking (EtOH), following cued fear conditioning and extinction, impacts fear expression in mice. Molecular (activity-regulated cytoskeleton-associated protein, Arc/arg3.1) and structural (dendrite and spine morphometry) markers of neuronal plasticity were measured following remote extinction retrieval. Mouse age (adolescent and adult) and sex were included as interacting variables in a full factorial design. Females drank more EtOH than males and adolescents drank more EtOH than adults. Adolescent females escalated EtOH intake across drinking days. Adolescent drinkers exhibited more conditioned freezing during extinction retrieval, an effect that persisted for at least 20 days. Heightened cued freezing in the adolescent group was associated with greater Arc/arg3.1 expression in layer (L) 2/3 prelimbic (PL) cortex, greater spine density, and reduced basal dendrite complexity. In adults, drinking was associated with reduced L2/3 infralimbic (IL) Arc expression but no behavioral differences. Few sex interactions were uncovered throughout. Overall, these data identify prolonged age-related differences in alcohol-induced fear extinction impairment and medial prefrontal cortex neuroadaptations.

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  • Recent studies have reported deficits in recall of an extinguished fear response, deficits in reversal learning, and impaired working memory following adolescent alcohol exposure.

    “Recent studies have reported deficits in recall of an extinguished fear response [54], deficits in reversal learning [43], and impaired working memory [55, 56] following AAE.”

    From Consequences of adolescent drug use (2023) · cites this paper as [54]

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  1. Yuste R, 2010. Dendritic spines. MIT press.

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Authors
Lawson, K., Scarlata, M. J., Cho, W. C., Mangan, C., Petersen, D., Thompson, H. M., Ehnstrom, S., Mousley, A. L., Bezek, J. L., & Bergstrom, H. C.
Affiliations
Vassar College (US)
Corresponding author
Bergstrom, H.C.
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2022-06
Volume
211
Pages
109048
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2022.109048
PMC
PMC9067297
OpenAlex
W4221103611
Cited by
16
References
110
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 5
FWCI
1.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropharmacology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIAAA (P50 AA017823)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
adolescent alcohol exposure, fear extinction, fear conditioning, post-traumatic stress disorder, alcoholism, medial prefrontal cortex, Arc/Arg3.1, dendritic spine density, prelimbic cortex, infralimbic cortex, sex differences, age differences, traumatic memory, conditioned freezing
MeSH terms
Adolescent, Ethanol, Animals, Extinction, Psychological, Fear, Female, Humans, Male, Stress Disorders, Post-Traumatic, Prefrontal Cortex, Mice

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