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

Abstract

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.

Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm

“…In rodent studies, rat pups born to parents who were both exposed to THC during adolescence had increased heroin-seeking behaviour later in life, a phenotype that was accompanied by epigenetic changes in the nucleus accumbens [13][14][15]. These studies and others have begun to highlight the potential for intergenerational consequences of cannabis exposure [16]. CONTACT Identifying the mechanism that underlies these changes is critical as cannabis use continues to increase across the U.S.…”

Who's your daddy? Behavioral and epigenetic consequences of paternal drug exposure

“…Adolescent paternal exposure to the synthetic cannabinoid receptor agonist WIN55,212‐2 (WIN) did not alter locomotor activity in adult SD offspring at baseline or after unpredictable stress (Ibn Lahmar Andaloussi et al, 2019). Adult THC‐sired offspring showed more rapid habituation of locomotor activity relative to control‐sired offspring; this effect was not seen in adolescent offspring (Levin et al, 2019).…”

“…Adult THC‐sired offspring showed more rapid habituation of locomotor activity relative to control‐sired offspring; this effect was not seen in adolescent offspring (Levin et al, 2019). Additionally, episodic memory was unchanged in WIN‐sired offspring relative to control offspring as measured by the object recognition test (Ibn Lahmar Andaloussi et al, 2019). No effect of adolescent paternal THC exposure was seen on the novel object recognition test of non‐spatial memory (Levin et al, 2019).…”

“…Adolescent THC exposure in males did not alter anxiety‐like behavior in offspring on the elevated plus maze (Levin et al, 2019). While WIN‐ and control‐sired offspring do not differ on open field anxiety measures, WIN‐sired offspring show greater unpredictable stress‐induced anxiety‐like behaviors relative to control‐sired offspring (Ibn Lahmar Andaloussi et al, 2019). THC‐sired offspring do not differ from control‐sired offspring in fear response as measured by the novelty suppressed feeding task (Levin et al, 2019).…”

“…Offspring of WIN‐exposed sires show differential changes on DNMT's and stress hormones prior to and after stress exposure (Ibn Lahmar Andaloussi et al, 2019). Corticosterone levels do not differ between WIN‐ and control‐sired offspring at baseline or after chronic unpredictable stress.…”