Long-lasting effects of prenatal delta-9-tetrahydrocannabinol exposure in young rat offspring

Consumption of cannabinoid-containing products has increased for their beneficial effects on pregnancy for reducing symptoms such as nausea, vomiting or anxiety. However, FDA clearly strongly advises against the use of delta-9-tetrahydrocannabinol (THC) during pregnancy. Alongside, mostly of the studies have investigated the effects of prenatal THC (pTHC) exposure, in males only, but pTHC shows a sex bias. Here, we investigate the effects of pTHC exposure in the male and female young rats.Sprague and Dawley rats were subcutaneously treated with THC (2 mg/kg/day) or vehicle (VHC), from gestational day (GD) 5 to GD 20 and the young offspring were tested for recognition memory and sociability in the novel object recognition test and in the social interaction test.The gene expression levels of endocannabinoid/dopaminergic system elements were analyzed in the prefrontal cortex by RT-PCR. Young pTHC exposed rats of both sexes exhibited deficits both in object recognition memory (p<0.001) and in the sociability (p<0.001), which alterations were paralleled by increased CB1R (p<0.05) and DAGL-alfa (p<0.05), D2DR (p<0.05) and decreased FAAH (p<0.05) mRNA levels, respectively. We also analyzed the related immune effects of pTHC on the blood immune offspring repertoire trough flow cytometry and there were no changes in the % of cells peripheral blood leukocytes between prenatal VHC exposed group and pTHC rats. Our data shows that pTHC is associated with a vulnerable phenotype characterized of cognitive and social impairment and altered tone of the endocannabinoid/dopaminergic system suggesting novel targets for future pharmacological approaches.