Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in schizophrenia: Analyses in patients and in perinatal ?9-tetrahydrocannabinol-exposed rats

Perinatal exposure to ?9-tetrahydrocannabinol (THC) affects brain development and might increase the incidence of psychopathology later in life, which seems be related a dysregulation endocannabinoid and/or dopaminergic systems. We here evaluated transcriptional regulation genes encoding for cannabinoid CB1 receptor (Cnr1) dopamine D2 (Drd2) perinatal THC-(pTHC) exposed male rats, focusing on role DNA methylation analyzed by pyrosequencing. Simultaneously, molecular behavioral abnormalities at two different time points (i.e., neonatal age adulthood) potential preventive effect peripubertal treatment with cannabidiol, non-euphoric component Cannabis, were assessed. The DRD2 was also cohort subjects schizophrenia. observed an both Cnr1 Drd2 mRNA levels selectively prefrontal cortex adult pTHC-exposed rats consistent reduction regulatory region, paralleled social withdrawal cognitive impairment reversed cannabidiol treatment. These preceded delayed appearance reflexes, higher lower 2-arachidonoylglycerol (2-AG) levels, persisted till adulthood. Alterations epigenetic mark found Overall, reported data add further evidence dopamine-cannabinoid interaction terms CNR1 could implicated pathogenesis schizophrenia spectrum disorders, suggesting that may normalize pTHC-induced modulating altered activity.