Periconceptional maternal alcohol consumption leads to behavioural changes in adult and aged offspring and alters the expression of hippocampal genes associated with learning and memory and regulators of the epigenome.

Maternal alcohol consumption throughout pregnancy can result in long term behavioural deficits in offspring. However, less is known about the impact of alcohol during the periconceptional period (PC). The aim of this study was to examine the effect of PC ethanol (PC:EtOH) exposure on long term cognitive function; including memory and anxiety. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol;vol) or a control diet from 4 days prior to mating until day 4 of pregnancy. Separate cohorts of animals were tested at 6 months (adult) or 15-18 months of age (aged). Offspring underwent a series of behavioural tests to assess anxiety, spatial and recognition memory. The hippocampus was collected, and mRNA expression of epigenetic modifiers and genes implicated in learning and memory were examined. PC:EtOH exposure resulted in a subtle anxiety like behaviour in adult female offspring with a significant reduction in directed exploring/head dipping behaviour during holeboard testing. In aged male offspring, PC:EtOH exposure resulted in a tendency for increased directed exploring/head dipping behaviour during holeboard testing. No differences between treatments were observed in the elevated plus maze. Aged female offspring exposed to PC:EtOH demonstrated short term spatial memory impairment (P < 0.05). PC:EtOH resulted in an upregulation of hippocampal mRNA expression of bdnf, grin2a and grin2b at 18 months of age along with increased expression of epigenetic modifiers (dnmt1, dnmt3a and hdac2). In conclusion, PC:EtOH can lead to sex specific anxiety-like behaviour and impairments in spatial memory and altered hippocampal gene expression.

The impact of periconceptional alcohol exposure on fat preference and gene expression in the mesolimbic reward pathway in adult rat offspring.

Alcohol consumption around the time of conception is highly prevalent in Western countries. Exposure to ethanol levels during gestation has been associated with altered development of the mesolimbic reward pathway in rats and increased propensity to addiction, however the effect of exposure only around the time of conception is unknown. The current study investigated the effects of periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food preferences and gene expression in the ventral tegmental area (VTA) and the nucleus accumbens of the adult offspring. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol/vol) or a control diet from 4 days before mating until 4 days after mating. PC:EtOH had no effect on alcohol preference in either sex. At 15 months of age, however, male PC:EtOH offspring consumed more high-fat food when compared with male control offspring, but this preference was not observed in females. Expression of the dopamine receptor type 1 (Drd1a) was lower in the VTA of male PC:EtOH offspring compared with their control counterparts. There was no effect of PC:EtOH on mRNA expression of the µ-opioid receptor, tyrosine hydroxylase (Th), dopamine receptor type 2 (Drd2) or dopamine active transporter (Slc6a3). These data support the hypothesis that periconceptional alcohol exposure can alter expression of key components of the mesolimbic reward pathway and heighten the preference of offspring for palatable foods and may therefore increase their propensity towards diet-induced obesity. These results highlight the importance of alcohol avoidance when planning a pregnancy.