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Study · Animal study (in vivo) · mouse · 2025

3 results

Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.

Wang Y, Yue S, Yang F, Chen L, Singh A, Marciniak M, Wei W, Wang ZJ

Nature communications29 Oct 2025Cited by 5 (Europe PMC)

PMID41162376 (opens in a new tab)PMCIDPMC12572406 (opens in a new tab)DOI10.1038/s41467-025-64585-7 (opens in a new tab)PepBankPUB-41162376
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Summary

Early-life adversities increase vulnerability to substance use disorders, which are characterized by persistent, uncontrollable drive to seek drugs, often leading to relapse. Previously, we reported that early social isolation (ESI) during adolescence potentiates heroin-seeking in mice. However, the underlying neurobiology remains unknown. Here, we found that ESI aggravated heroin-induced neuronal dysfunction in prelimbic cortex (PrL) to ventral tegmental area (VTA) projecting neurons. Activating PrL->VTA projection attenuated ESI-potentiated heroin seeking, alongside normalized neuronal function. RNA-seq revealed that ESI and heroin convergently altered genes regulating morphogenesis and metabolism, with Tmsb4x (thymosin β4) as a key gene. ESI and heroin interaction affected genes regulating cell cycle and DNA damage response, with Mcm3 and Mcm7 (minichromosome maintenance proteins 3/7) as hubs. PrL thymosin β4 infusion or CRISPR-Cas9-mediated PrL->VTA projection-specific Mcm3/7 knockdown attenuated ESI-potentiated heroin-seeking and neuronal hypofunction. Our study suggests that ESI-potentiated heroin relapse is associated with neuronal and transcriptional alterations in PrL->VTA projection.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

2 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice, infusion of thymosin β4 into the prelimbic cortex attenuated early social isolation (ESI)-potentiated heroin seeking.

    In plain wordsIn mice, thymosin beta‑4 infused into a brain area reduced the extra heroin seeking caused by early social isolation.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    DecreaseESI-potentiated heroin seeking
    Study

    mousen: not reported in source

    early social isolation heroin-seeking model
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    Dose not stated · infusion into prelimbic cortexAs given in this study (mouse).

    Source sentences

    Summary
    PrL thymosin β4 infusion or CRISPR-Cas9-mediated PrL->VTA projection-specific Mcm3/7 knockdown attenuated ESI-potentiated heroin-seeking and neuronal hypofunction.
    1 context sentence
    Title · context
    Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice, infusion of thymosin β4 into the prelimbic cortex attenuated neuronal hypofunction linked to early social isolation and heroin.

    In plain wordsIn mice, thymosin beta‑4 infused into a brain area reduced the weak nerve cell activity linked to early social isolation and heroin.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    DecreaseNeuronal hypofunction in PrL->VTA projection
    Study

    mousen: not reported in source

    early social isolation heroin-seeking model
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    Dose not stated · infusion into prelimbic cortexAs given in this study (mouse).

    Source sentences

    Summary
    PrL thymosin β4 infusion or CRISPR-Cas9-mediated PrL->VTA projection-specific Mcm3/7 knockdown attenuated ESI-potentiated heroin-seeking and neuronal hypofunction.
    1 context sentence
    Title · context
    Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 03AnimalEndogenous levelAnimal study (in vivo)Mechanism

    In mice, RNA-seq showed that early social isolation and heroin convergently altered genes regulating morphogenesis and metabolism, with Tmsb4x (thymosin β4) as a key gene.

    In plain wordsIn mice, the gene for the body's own thymosin beta‑4 was among genes changed by early social isolation and heroin.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    Direction not reportedTmsb4x expression after early social isolation and heroin
    Study

    mousen: not reported in source

    Outcome group
    Receptor activity and mechanism · Mental health and mood

    Source sentences

    Summary
    RNA-seq revealed that ESI and heroin convergently altered genes regulating morphogenesis and metabolism, with Tmsb4x (thymosin β4) as a key gene.
    1 context sentence
    Title · context
    Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.

    This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 01:52 UTC

    Study results updated

  2. Version 1

    12 Oct 2026, 18:17 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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