Prenatal Infection Plus Adolescent THC Leaves Hidden Brain Changes in Rats

While adolescent THC did not trigger visible behavioral disruptions, PET brain scans revealed alterations dependent on the combination of prenatal immune activation and THC. Gene expression analysis showed maternal immune activation affected dopamine, glutamate, and serotonin genes, with the two-hit combination shifting expression from downregulation to upregulation. Blood biomarkers of inflammatory pathway changes were identified.

Two-hit animal model combining maternal immune activation with adolescent THC exposure in male and female rats, followed by behavioral testing, longitudinal PET neuroimaging, RNA sequencing of orbitofrontal cortex and blood cells.

This is the first study to show that the combination of prenatal immune challenge and adolescent THC leaves detectable molecular and neuroimaging marks even before behavioral symptoms emerge, suggesting a hidden vulnerability window.

The "two-hit" hypothesis of schizophrenia suggests that prenatal insults create vulnerability that later environmental factors, like adolescent cannabis use, can trigger. This study shows the combination leaves biological traces even without overt symptoms.

Animal model of immune activation may not fully replicate human prenatal infection. THC doses may not reflect human use patterns. Behavioral effects may emerge later than the observation window. Blood biomarkers need human validation.