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An adolescent hangover: astrocyte dysfunction in paraventricular thalamus promotes adult anxiety after alcohol exposure in adolescent mice

Neuropsychopharmacology (2025)Cite this article

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While non-harmful alcohol consumption is common in adulthood, the time when an individual begins drinking has a profound impact on later life. Problematic alcohol use during adolescence typically involves bouts of heavy binging, and repeated binging leads to increased risk for developing anxiety disorders [1]. In clinical studies, it is difficult to dissociate the link between pre-existing anxiety disorders and adolescent alcohol use, but this potential link can be studied using preclinical rodent models. In this issue of Neuropsychopharmacology, Bennett et al. [2] used an intermittent repeated ethanol exposure (AIE) model to test whether adolescent alcohol exposure increases anxiety-related behaviors in adulthood, and whether changes in regulation of the glutamate transporter 1 (GLT1) by astrocytes in the paraventricular nucleus of the thalamus (PVT) is critical to this effect. PVT is a critical hub for integrating stress, arousal, and emotional information [3], and changes in PVT function have been linked to anxiety-like behaviors in rodent models [4].

Bennet et al. first showed that AIE in mice produces a persistent anxiety-like phenotype in adulthood. They found that mice subjected to ethanol exposure in a vapor inhalation chamber (postnatal day 28 to 46) and then given 4 weeks of withdrawal to achieve adulthood, had increased anxiety-like behavior in open field and elevated plus maze tests. In a key control condition, they show that this manipulation does not change general locomotor activity.

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Authors and Affiliations

  1. School of Pharmacy, Center for Neuroscience, University of Camerino, Via Madonna delle Carceri, Camerino, MC, Italy

    Gregorio Sonsini

  2. Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, The Netherlands

    Nathan J. Marchant

  3. Compulsivity Impulsivity and Attention, Amsterdam Neuroscience, Amsterdam, The Netherlands

    Nathan J. Marchant

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  1. Gregorio Sonsini
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  2. Nathan J. Marchant
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GS and NJM wrote the manuscript.

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Correspondence to Nathan J. Marchant.

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Sonsini, G., Marchant, N.J. An adolescent hangover: astrocyte dysfunction in paraventricular thalamus promotes adult anxiety after alcohol exposure in adolescent mice. Neuropsychopharmacol. (2025). https://doi.org/10.1038/s41386-025-02300-2

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