Personality-based intergenerational effects of prenatal THC exposure in an inherited mouse model of social dominance and submissiveness.
Mohamed Mari, Anastasia Bagaev, Debpali Sur, Beatriz G S Rocha, Dilorom Begmatova, Natalia Zemliana, Abdalla Bowirrat, Kenneth Blum, Panayotis K Thanos, Natalya M Kogan, Albert Pinhasov
Scientific Reports August 20, 2025 DOI: 10.1038/s41598-025-15528-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Selectively bred Dominant and Submissive mice offspring (generation 54) prenatally exposed to THC |
| Intervention | THC |
| Dose | 20 mg/kg, intraperitoneally, on gestation days 13, 15, and 17 |
| Duration | THC administered on gestation days 13, 15, and 17; offspring assessed at postnatal days 7 and 30 and at two months of age |
| Topics | Cannabis |
| Keywords | Dopaminergic system das Endocannabinoid system ecs Prenatal development Social behavior Stress resilience |
| Key findings | Prenatal THC reduced body weight at postnatal days 7 and 30 and produced phenotype-specific behavioral effects: increased anxiety-like behavior in resilient Dominant offspring but enhanced sociability and reduced anxiety-like behavior in vulnerable Submissive offspring. The authors report phenotype-specific changes in endocannabinoid and dopaminergic gene expression, including FAAH downregulation in Submissive offspring, and suggest that stress resilience does not necessarily protect against prenatal THC's adverse effects. |
Abstract
This study examines how stress-coping phenotypes influence the effect of prenatal [Formula: see text]9-tetrahydrocannabinol (THC) exposure (PTE) on selectively bred Dominant (Dom) and Submissive (Sub) mice offspring exhibiting stress resilience and vulnerability, respectively. Pregnant Dom and Sub dams of generation 54 received THC (20 mg/kg, intraperitoneally) on gestation days 13, 15, and 17. Our findings indicate that PTE significantly reduced body weight (measured at postnatal day (PND) 7 and 30), increased anxiety-like behaviors in two-month-old Dom offspring, and enhanced sociability and reduced anxiety-like behaviors in Sub offspring. Brain mRNA expression analysis revealed phenotype-specific alterations in endocannabinoid (ECS) and dopaminergic (DAs) system genes. Remarkably, fatty acid amide hydrolase (FAAH) expression, responsible for anandamide degradation, was downregulated in the prefrontal cortex and hippocampus of Sub PTE offspring on PND 7 and 30, alongside changes in CB1, CB2, D1, D2, and D5 receptors expression. Our findings suggest that the intergenerational effect of PTE depends on individual temperament, with ECS modulation during prenatal development offering a potential intervention for stress vulnerability. However, we state that stress resilience does not necessarily confer protection against PTE's adverse effects, emphasizing the complexity of cannabis exposure during pregnancy.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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and 2 more in the library