499. EFFECTS OF PRENATAL CANNABINOIDS EXPOSURE: ASSESSING THE ROLE OF THE ENDOCANNABINOID SYSTEM IN A NEURODEVELOPMENTAL ANIMAL MODEL OF PSYCHOPATHOLOGY

Abstract Background Consumption of Cannabis sativa derivatives has increased for their beneficial effects on pregnancy in reducing symptoms such as nausea, vomiting, insomnia and anxiety. However, FDA clearly strongly advises against the use of delta-9-tetrahydrocannabinol (THC) during pregnancy (Solowij et al., 2016). Aims & Objectives The current study was designed to examine the long-term effects of prenatal exposure to THC on the social, cognitive, and motor behaviors of male and female rat offspring throughout their lifespan. Method Sprague Dawley pregnant rats were subcutaneously treated with THC (2 mg/kg/day) or vehicle (VHC) from gestational day (GD) 5 to GD 20. Daily maternal bodyweight was measured from GD 3 to GD 21. Somatic growth and developmental milestones were assessed in the offspring from postnatal day 3 (PND 3) to PND 11. During adolescence, the offspring were tested for spontaneously locomotor activity, recognition memory and sociability in the open field test, in the novel object recognition test and in the social interaction test, respectively. mRNAs expression of endocannabinoidand dopaminergic system elements were evaluated in several brain regions of rats (Di Bartolomeo et al., 2021). We also analyzed the related immune effects of pTHC on the blood immune offspring repertoire using flow cytometry. Results THC did not affect maternal and pups body growth (at PND 3) but produced transient delays in the righting reflex and in eye opening time in male and female offspring. 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. There were no changes in the % of cells peripheral blood leukocytes between VHC treated group and pTHC rats. Discussion & Conclusions Our data shows that prenatal THC exposure leads to anomalies at neonatal age which may be considered as early markers of neurodevelopmental disorders later in life characterized by cognitive and social impairment. Furthermore, the altered tone of the endocannabinoid/dopaminergic system, may be suggested as potential target for innovative pharmacological challenges.