Prenatal THC Exposure Affected Mouse Offspring Differently Based on Their Inborn Temperament

In selectively bred dominant mice, prenatal THC exposure reduced body weight and increased anxiety-like behaviors. In submissive mice, THC exposure enhanced sociability and reduced anxiety. Brain analysis revealed temperament-specific changes in endocannabinoid and dopamine system genes, with FAAH expression notably downregulated in submissive offspring's prefrontal cortex and hippocampus.

Pregnant dominant and submissive mice (generation 54 of selective breeding) received THC (20 mg/kg IP) on gestation days 13, 15, and 17. Offspring were tested for anxiety, social behavior, and body weight. Brain mRNA expression of endocannabinoid system (CB1, CB2, FAAH) and dopaminergic system (D1, D2, D5) genes was analyzed at postnatal days 7 and 30.

This is the first study to show that the behavioral effects of prenatal THC depend on pre-existing temperament. The finding that THC exposure could either increase or decrease anxiety depending on the individual's baseline stress vulnerability has significant implications for understanding variable outcomes in human prenatal cannabis exposure.

Human studies of prenatal cannabis exposure show highly variable outcomes. This animal model suggests that individual genetic temperament may explain much of that variability. Stress-vulnerable individuals may actually respond differently to prenatal THC than stress-resilient ones, complicating simple warnings about cannabis use during pregnancy.

The mouse lines are selectively bred for extreme temperament traits that may not correspond to normal human variation. The THC dose (20 mg/kg) is relatively high. The specific behavioral tests may not translate directly to human outcomes. Only male offspring were tested.