Browsing by Author "Aarnio R."
  • Institution Publication
    Cannabidiol modulates brain molecular alterations, gut microbiota dysbiosis and alcohol self-administration in a mouse model of fetal alcohol spectrum disorder
    ( 2025-12-01)
    Navarrete F.
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    Navarrete F.
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    Navarrete F.
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    Cabrera-Rubio R.
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    Gasparyan A.
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    Gasparyan A.
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    Gasparyan A.
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    Aarnio R.
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    Aarnio R.
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    López-Picón F.
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    López-Picón F.
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    Helin S.
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    Rajander J.
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    Rajander J.
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    Collado M.C.
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    Manzanares J.
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    Manzanares J.
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    Manzanares J.
    Fetal Alcohol Spectrum Disorder (FASD) is a range of neurodevelopmental abnormalities caused by Perinatal Alcohol Exposure (PAE), leading to profound behavioral and molecular disturbances in the offspring. Unraveling the central and peripheral mechanisms involved, including the microbiota-gut-brain axis, is crucial to improving our understanding of the disease and developing new treatment strategies from a sex perspective. In this study, we investigated the impact of PAE on emotional behavior, brain biomarkers, and gut microbiota composition and diversity in a preclinical C57BL/6 J mouse model, as well as the extent of their vulnerability to alcohol consumption. Furthermore, we have also explored the potential modulatory effects of cannabidiol (CBD) administered chronically (30 mg/kg/day, i.p.) from weaning on PAE-induced sex-dependent emotional and brain molecular impairments, gut microbiota dysbiosis, and increased alcohol reinforcing and motivational actions. FASD model mice showed increased anxiety- and depressive-like behavior accompanied by sex-dependent changes in synaptic density, dopamine D2/D3 receptors availability, cannabinoid receptors 1 and 2 ( Cnr1/Cnr2 ), tyrosine hydroxylase ( Th ), and serotonin transporter ( Slc6a4) gene expression, and gut microbiota dysbiosis. Interestingly, CBD sex-dependently improved and/or normalized PAE-induced behavioral and molecular disturbances. In addition, females but not males exposed to the animal model of FASD showed a higher motivation to drink alcohol, which CBD abolished. Our findings provide new insights into the brain and gut microbiota sex-dependent mechanisms involved in FASD pathophysiology and further highlight the therapeutic potential of CBD to improve the management of FASD-induced emotional disturbances and alcohol addiction from a sex-oriented approach.