Evidence map›Paper›PMID 40666923›Full record

ArticlebioRxiv : the preprint server for biology2025

Early life stress modulates behavioral sensitivity to alcohol and promotes escalation of alcohol drinking.

Allison R Morningstar, Olivia S R Ledbury, Angeline C Yu, Haniyyah Sardar, Ethan T Rogers, Isaac F Kandil, R Nicolas Fajardo, Max E Benabou, William J Giardino

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Allison R MorningstarWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.ORCID 0000-0002-3857-0450
Olivia S R LedburyWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.
Angeline C YuWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.
Haniyyah SardarWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.
Ethan T RogersWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.
Isaac F KandilWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.
R Nicolas FajardoWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.
Max E BenabouWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.
William J GiardinoWu Tsai Neurosciences Institute and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.ORCID 0000-0001-7474-7914

Funding

Alcohol-related sleep disturbances and circuit dynamics of arousal neuropeptidesR00AA025677 · NIAAA · STANFORD UNIVERSITY · PI GIARDINO, WILLIAM J · 2021 to 2023
$915k
Extended amygdala corticotropin-releasing factor circuits mediating sex-specific impacts of early life stress on alcohol sensitivityF31AA031630 · NIAAA · STANFORD UNIVERSITY · PI Allison Rebecca Morningstar · 2024 to 2026
$129k
NIAAA NIH HHS F31 AA031630NIAAA NIH HHS R00 AA025677
6 · The paper itself

Abstract

Adverse childhood experiences significantly increase the risk of developing alcohol use disorder (AUD) in adulthood. We used a model of combined limited bedding/nesting and maternal separation (LBN+MS) in C57BL/6J background mice to investigate how early life stress (ELS) modulates behavioral sensitivity to alcohol, long-term alcohol drinking patterns, and the effects of alcohol on social behaviors. Our findings reveal that ELS increased sensitivity to the stimulatory locomotor effects of alcohol (1.75 g/kg) selectively in females and reduced sensitivity to the sedative effects of alcohol (4.0 g/kg) particularly in males. This pattern of enhanced stimulation and diminished sedation is consistent with phenotypes observed in human subjects at high risk for developing AUD. ELS also significantly enhanced escalation of voluntary alcohol intake and preference over eight weeks of two-bottle choice intermittent access drinking particularly in males. Additionally, social behavior assessments revealed that ELS impaired sociability selectively in females with a history of alcohol drinking, highlighting the detrimental interactive effects of ELS and alcohol exposure on adaptive behaviors. These results underscore the complex interplay between ELS, alcohol responses, and sex differences, suggesting that ELS creates a high-risk phenotype for AUD through altered alcohol behavioral sensitivity. Our study highlights the importance of future studies that seek to identify the neurobiological mechanisms underlying these interactions, which may pave the way for targeted interventions in populations affected by childhood adversity and excessive alcohol consumption.

Identifiers

PMID40666923
PMCPMC12262304

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.