Adolescent Δ9-tetrahydrocannabinol exposure differently affects histone modifications in the brain of female and male rats

Despite the increasing evidence of a possible interaction between adolescent Cannabis abuse and the subsequent development of psychiatric disorders, Cannabis remains the illicit drug most abused by adolescents. We have previously demonstrated that female rats chronically treated during adolescence with increasing doses of delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient of cannabis, develop a depressive/psychotic-like phenotype in adulthood. Interestingly, only chronic adolescent exposure to THC, but not adult exposure, led to this complex phenotype, suggesting that adolescence may represent a more vulnerable period for the adverse effect of THC. However, the neurobiology of this vulnerability is not still clear. Considering the important role assumed by epigenetics in the etiopathogenesis of psychiatric disorders, the main goal of this thesis is to extend our knowledge on the impact of adolescent THC exposure on histone modifications occurring in other brain areas involved in the different aspects of the depressive/psychotic-like phenotype described in our animals. Specifically, we considered the Hippocampus for its involvement in cognition, the Nucleus Accumbens for its role in the reward circuit, and the Amygdala for its relevance in the emotional behaviour. To investigate the existence of age-specificity of THC effects, we performed the same analysis also after adult THC treatment. To investigate sex-dependency of THC response, we also checked THC response in adolescent male animals. First of all, adolescent (PND 35-45) and adult (PND 75-85) female Sprague-Dawley rats were treated twice a day with increasing intraperitoneal (ip) doses of THC: 2.5 mg/kg, 5 mg/kg, and 10 mg/kg or with its vehicle. Two, 24 and 48 hours after the end of the treatment, the brain areas of interest were collected and. Histone modifications associated with both transcriptional repression (H3K9 di- and tri-methylation, H3K27 trimethylation) and activation (H3K9 and H3K14 acetylation) were evaluated. Chronic THC ...