Evidence map›Paper›PMID 42252467›Full record

ArticleBiology of sex differences2026

Maternal deprivation and adolescent alcohol exposure induce sex-dependent alterations in stress-related behavior and lipid signaling in rats.

Laura Sánchez-Marín, Adriana Castro-Zavala, María Flores-López, Ana Gavito, Raquel Reviriego, Eva M Marco, Francisco J Pavón-Morón, Fernando Rodríguez de Fonseca, Antonia Serrano

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Article in Biology of sex differences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Laura Sánchez-Marín *IBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Málaga, Spain.
Adriana Castro-Zavala *IBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Málaga, Spain.
María Flores-López *IBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Málaga, Spain.
Ana GavitoIBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Málaga, Spain.
Raquel ReviriegoIBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Málaga, Spain.
Eva M MarcoFacultad de Ciencias Biológicas, Departamento de Genética, Fisiología y Microbiología, Universidad Complutense, Madrid, Spain.
Francisco J Pavón-MorónIBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Málaga, Spain.
Fernando Rodríguez de FonsecaIBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Málaga, Spain. fernando.rodriguez@ibima.eu.
Antonia SerranoIBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Málaga, Spain. antonia.serrano@ibima.eu.

Funding

Instituto de Salud Carlos III PI22/00427 and RD24/0003/0012Instituto de Salud Carlos III PI22/01833Instituto de Salud Carlos III PI25/02025 and FORT23/ 00013
6 · The paper itself

Abstract

backgroundEarly-life stress constitutes a major risk factor for the development of neuropsychiatric and substance use disorders, exerting enduring effects on stress responsivity and emotional behavior. Maternal deprivation (MD) is a well-established model of early adversity that induces persistent neurobiological alterations. During adolescence, alcohol exposure presents an additional challenge that may interact with early-life stress, potentially influencing long-term adaptations in a sex-dependent manner. Among the systems involved, lipid signaling pathways, including the endocannabinoid system (ECS) and lysophosphatidic acid (LPA) signaling, have emerged as key regulators of stress adaptation.

methodsMale and female Wistar rats were subjected to a single 24-h MD episode on postnatal day 9 (PND9). During adolescence (PND31-55), animals received intermittent alcohol exposure (3 g/kg) or saline. Behavioral assessments included the forced swim test and elevated plus maze. Plasma levels of corticosterone, monoacylglycerols, N-acylethanolamines, LPA, and autotaxin were measured. Concurrently, mRNA expression of genes encoding ECS- and LPA-related receptors, as well as enzymes involved in the metabolism of these lipid signaling pathways, was analyzed in the medial prefrontal cortex (mPFC). Data were evaluated using three-way ANOVA with sex, MD, and adolescent alcohol exposure as factors.

resultsMD induced persistent metabolic alterations and revealed sex-specific effects on alcohol pharmacokinetics, with increased blood alcohol concentrations in MD females. Behavioral analyses demonstrated sex-dependent effects, with MD increasing active coping in males and decreasing it in females, while enhancing open-arm exploration independently of adolescent alcohol exposure. Adolescent alcohol exposure increased plasma corticosterone levels. MD and sex significantly altered circulating lipid mediators, showing opposite patterns in males and females. Additionally, MD and adolescent alcohol exposure differentially modulated the expression of ECS- and LPA-related genes in the mPFC, indicating sex-dependent molecular adaptations.

conclusionsEarly-life stress establishes long-lasting, sex-specific alterations in behavioral and lipid-mediated stress responses. Adolescent alcohol exposure acts as a secondary challenge, unmasking or amplifying these adaptations. The integration of peripheral lipid profiles with mPFC molecular changes highlights lipid signaling pathways as key mediators linking early adversity and adolescent experiences with long-term vulnerability to stress-related psychopathology.

Indexed as

Behavior, AnimalEthanolLipid MetabolismMaternal DeprivationSex CharacteristicsStress, PsychologicalAnimalsCorticosteroneFemaleMaleRatsRats, WistarSignal TransductionCorticosteroneEthanolAdolescenceAlcoholLipid mediatorsMaternal deprivationSexual dimorphism

Identifiers

PMID42252467
PMCPMC13255284

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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.