ArticleStress (Amsterdam, Netherlands)2016
Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABA(A) mechanism.
Article in Stress (Amsterdam, Netherlands), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Developmental history, energetic state and choice impulsivity in European starlings, Sturnus vulgaris.Animal cognition · 2019Pooled it
- Medium-intensity aerobic exercise can relieve mice anxiety by activating cannabinoid type 1 receptors on medial prefrontal cortex GABAergic neurons.Translational psychiatry · 2026Article
- Combined maternal separation and limited bedding-nesting increase goal tracking, delay discounting, and impulsive action, and moderate sign-tracking-perseverance associations in male rats.BMC neuroscience · 2026Article
- MRI assessment of intrinsic neural timescales in male alcohol use disorder patients.Frontiers in psychiatry · 2026Article
- The sleep-anxiety dysregulation model of alcohol use disorder risk: A nine-year longitudinal machine learning study.Journal of affective disorders · 2025Review
- The link between early-life adversity and later alcohol use disorder: A role for microglia?Neurobiology of stress · 2025Article
- Region-specific neuroadaptations of CRF1 and CRF2 expression following heroin exposure in female rats.Pharmacology, biochemistry, and behavior · 2025Article
- Neurobiological intersections of stress and substance use disorders.Frontiers in neuroscience · 2025Review
- Emotional neglect in childhood modulates aperiodic offset in the left pars orbitalis in adulthood.Frontiers in neuroscience · 2025Article
- Identification of Critical Signature in Post-Traumatic Stress Disorder Using Bioinformatics Analysis and in Vitro Analyses.Brain and behavior · 2025Article
- Early Life Stress and Major Depressive Disorder-An Update on Molecular Mechanisms and Synaptic Impairments.Molecular neurobiology · 2024Review
- GABA system as the cause and effect in early development.Neuroscience and biobehavioral reviews · 2024Review
- The role of brain serotonin signaling in excessive alcohol consumption and withdrawal: A call for more research in females.Neurobiology of stress · 2024Article
- Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.Gene & protein in disease · 2024Article
- Early life stress and body-mass-index modulate brain connectivity in alcohol use disorder.Translational psychiatry · 2024Article
- Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats.Neurobiology of stress · 2024Article
- Sex differences in addiction-relevant behavioral outcomes in rodents following early life stress.Addiction neuroscience · 2023Article
- Early-life stress biases responding to negative feedback and increases amygdala volume and vulnerability to later-life stress.Translational psychiatry · 2023Article
- Social and Behavioral Pathways between Adverse Childhood Experiences and Poor Adult Physical Health: Mediation by Early Adulthood Experiences in a Low-Income Population.International journal of environmental research and public health · 2022Article
- Alcohol Deprivation Differentially Changes Alcohol Intake in Female and Male Rats Depending on Early-Life Stressful Experience.NeuroSci · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2β3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the development of impulsivity and excessive alcohol consumption.
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Registered trials
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.