Behavioural and epigenetic effects of paternal exposure to cannabinoids during adolescence on offspring vulnerability to stress

Chronic cannabinoid exposure during adolescence in male rats induces chronic cognitive and emotional impairments. However, the impact of this form of exposure on offspring vulnerability to stress is unknown. The aim of this study was to evaluate the behavioural and epigenetic effects of stress in the offspring of male rats whose fathers were exposed to cannabinoids during adolescence. Male adolescent offspring of Win55,212-2 (1.2 mg/kg) treated rats were exposed during one week to variable stressors and subjected to behavioural tests of anxiety and episodic-like memory, followed by an assessment of global DNA methylation and expression of DNA methyltransferases enzymes DNMT1 and DNMT3a mRNA in the prefrontal cortex. Stress exposure induced a significant anxiogenic-like effect but did not affect the episodic-like memory in the offspring of Win55,212-2 exposed fathers in comparison to the offspring of non-exposed fathers. These behavioural changes were subsequent to a significant increase in global DNA methylation and DNMT1 and DNMTa3 transcription in the prefrontal cortex. These data suggest that the deleterious effect of chronic exposure to cannabinoids during adolescence are not limited to the exposed individuals but may increase the vulnerability to stress-induced anxiety in the offspring and alter their epigenetic programming.