Genetics and epigenetics: paternal adolescent ethanol consumption in serotonin transporter knock-out rats and offspring sensitivity to ethanol.

RATIONALE: Alcohol use disorder (AUD) is shown to have an overall heritability of around 50%. One of the genes associated with AUD is SLC6A4 (solute carrier family 6 member A4) which codes for the serotonin transporter (SERT). The study looked at serotonin dysfunction on ethanol consumption in adolescents and the subsequent intergenerational effects of drinking by using a rat model: SERT+/+ (regular functioning), SERT+/- (50% transporter reduction) and SERT-/- (complete reduction). OBJECTIVES: We investigated sex and genotype differences in ethanol consumption in SERT knock-out Wistar rats (F0) followed by studying behaviour in the offspring (F1) of the male drinkers to assess effects of paternal alcohol consumption. METHODS: An intermittent access two-bottle choice paradigm (IA2BC) was used to yield ethanol drinking behaviour in F0 adolescent Wistar rats. The highest drinking males were mated to alcohol-naive females and their offspring were compared with controls. Drinking behaviour (IA2BC) and ethanol-induced motor coordination effects (via rotarod) were measured in the F1s. RESULTS: F0 drinking saw no SERT genotype differences in males. However, females consumed higher volumes of ethanol compared to males, with SERT-/- females showing the highest intake. A clearer genotype effect was seen in the F1 animals, with reduction in SERT activity leading to enhanced ethanol intake in both sexes. Importantly, paternal exposure to ethanol significantly reduced the ethanol induced motor side effects in offspring, independent of sex and genotype. CONCLUSIONS: These indicate a difference in the way genetic factors may act across sexes and suggest the involvement of epigenetic mechanisms in the intergenerational effects of alcohol.

Future preferences and prospection of future of outcomes: Independent yet specific associations with attention-deficit/hyperactivity disorder.

INTRODUCTION: Symptoms of attention-deficit hyperactivity disorder (ADHD) and conduct problems have been associated with heightened temporal discounting of reward value resulting in a preference for immediate over delayed outcomes. We examined the cross-sectional relationship between future preference (including intertemporal choice) and prospection (the ability to bring to mind and imagine the experience of future personally-relevant events and outcomes) in adolescents with a range of ADHD symptoms and aggressive behaviour. METHODS: A combination of behavioural tasks and self-reports measured intertemporal decision making, individual differences in preference for future outcomes and experience of prospection in a convenience sample of English adolescents aged 11-17 (n = 64, 43.8% males). Parents rated symptoms of ADHD and aggression. RESULTS: & Conclusions: Factor analysis identified two factors: "Future Preference" and "Prospection". Significant negative bivariate correlations were found between ADHD and the scores of both factors and between aggression and Future Preference. A path model confirmed the independent significant association of ADHD with both factors but not with aggression. There was no evidence that Prospection was associated with Future Preference or that it reduced the associations between ADHD symptoms and Future Preference. These results provide further evidence that ADHD is associated with a tendency to prefer immediate over future outcomes. The same association with aggression seemed to be driven by the overlap with ADHD symptoms. We provide some of the first evidence that individuals with high ADHD symptoms have difficulty in prospecting about future episodes. However, this is unrelated to their preference for future outcomes.