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<p>Exposure to valproic acid (VPA) during early pregnancy has been noted to show classical signs of autism. This study examined the potential efficacy of cannabidiol (CBD) in addressing a range of autism-like behaviours. Specifically, we investigated CBD’s impact on repetitive behaviours, social interaction deficits, and alterations in GABAergic neurons and cannabinoid 1 receptor (CB1R) expression in the hippocampus and medial prefrontal cortex, following prenatal VPA exposure in young C57BL/6&#xa0;J mice. To induce autism-like behaviours, pregnant mice received an intraperitoneal injection of sodium valproate (600&#xa0;mg/kg) on embryonic day (E) 12.5. Graded doses of oral CBD were administered (10&#xa0;mg/kg and 25&#xa0;mg/kg) to the offspring from post-natal day (PND) 21 to 34. Behavioural assessments included the marble-burying test, self-grooming test, and social interaction test. The animals were sacrificed at PND 35, and the brain tissues were fixed for 24&#xa0;h followed by the immunostaining process for demonstration of hippocampal and medial prefrontal cortex GABAergic neurons and cannabinoid 1 receptor (CB1R). CBD treatment (10&#xa0;mg/kg and 25&#xa0;mg/kg) significantly improved repetitive behaviours and social interaction deficits. Additionally, CBD reversed the significantly dysregulated expression of PV + GABAergic neurons and CB1R in the VPA-exposed mice to levels comparable to the control groups. These findings suggest that CBD mitigates molecular and behavioural alterations in a prenatal VPA-exposed animal model, highlighting its potential as a therapeutic agent for autism spectrum disorder.</p>

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Cannabidiol alleviates valproic acid-induced developmental changes in mice pups: role of the allosteric modulation of the CB1 receptor in the regulation of the GABAergic system

  • 期刊论文

  • 发表日期：

    2025年2月1日

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  • Princewill Sopuluchukwu Udodi,
  • Augustine Uche Agu,
  • Nto Johnson,
  • Roseline Ebube Udodi,
  • Chinyere N. Anyanwu,
  • Godson Emeka Anyanwu

摘要

Exposure to valproic acid (VPA) during early pregnancy has been noted to show classical signs of autism. This study examined the potential efficacy of cannabidiol (CBD) in addressing a range of autism-like behaviours. Specifically, we investigated CBD’s impact on repetitive behaviours, social interaction deficits, and alterations in GABAergic neurons and cannabinoid 1 receptor (CB1R) expression in the hippocampus and medial prefrontal cortex, following prenatal VPA exposure in young C57BL/6 J mice. To induce autism-like behaviours, pregnant mice received an intraperitoneal injection of sodium valproate (600 mg/kg) on embryonic day (E) 12.5. Graded doses of oral CBD were administered (10 mg/kg and 25 mg/kg) to the offspring from post-natal day (PND) 21 to 34. Behavioural assessments included the marble-burying test, self-grooming test, and social interaction test. The animals were sacrificed at PND 35, and the brain tissues were fixed for 24 h followed by the immunostaining process for demonstration of hippocampal and medial prefrontal cortex GABAergic neurons and cannabinoid 1 receptor (CB1R). CBD treatment (10 mg/kg and 25 mg/kg) significantly improved repetitive behaviours and social interaction deficits. Additionally, CBD reversed the significantly dysregulated expression of PV + GABAergic neurons and CB1R in the VPA-exposed mice to levels comparable to the control groups. These findings suggest that CBD mitigates molecular and behavioural alterations in a prenatal VPA-exposed animal model, highlighting its potential as a therapeutic agent for autism spectrum disorder.