It has long been established that excessive alcohol consumption during gestation can lead to a combination of growth deficiency, physical malformations and severe mental retardation known as Fetal Alcohol Syndrome (FAS). However, FAS is at the severe end of a wide range of disorders and deficits, associated with prenatal alcohol exposure, grouped together under the umbrella term Fetal Alcohol Spectrum Disorders (FASD). Included under the FASD heading are dysfunctions or deficits in learning and memory, attention, hyperactivity, social conduct, anxiety and depression which have been associated with exposure to alcohol in a range of doses, largely within the moderate to high region, as well as at varying stages of gestational development.
Taking this into account, many countries around the world officially recommend that women completely abstain from the consumption of alcohol during pregnancy and while breast feeding. However, many women consume alcohol while pregnant, with a large proportion of these women doing so in low to moderate amounts. Despite this, very little research has investigated the effects of prenatal exposure to alcohol within the low to moderately low dose range. This study aimed to use a rat model to investigate the long term cognitive and behavioural consequences of chronic low dose ethanol exposure for the duration of pregnancy in the rat which is the gestational period equivalent to the first two trimesters of human development.
Pregnant Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol) ethanol (15% EDC) or an isocaloric control diet for the duration of pregnancy. Male and Female prenatal ethanol treated and control offspring underwent behavioural testing at 7-10 months (Adult) or 15-18 months (Aged) of age. Aspects of anxiety like behaviour were assessed using Elevated Plus Maze (EPM), Holeboard (HB) and Emergence tests and social behaviour was assessed using a Social Interaction (SI) test. Learning and memory function was assessed using Morris Water Maze (WM) and Y maze tasks. An Ethanol Preference test (EPT) was also carried out using a standard two bottle choice paradigm. Stereological and morphological analyses of the amygdaloid complex and the hippocampus were conducted using Nissl and Golgi cox staining techniques.
This study found no significant effects of low dose prenatal alcohol exposure on ethanol preference. Similarly, there was no significant effect of low dose prenatal alcohol exposure on aspects of learning and memory function or pyramidal cell number in the CA1 or CA3 regions of the hippocampus. However, offspring prenatally exposed to low doses of ethanol were found to have a positive phenotype for anxiety-like behaviour in the EPM, HB and Emergence tests. This anxiety-like behaviour could not be attributed to alterations in pyramidal cell number within the amygdaloid complex, but rather was associated with an increase in synaptic connectivity within the BLA indicated by the significant increase in dendritic spine density along the apical dendrites of pyramidal cells within this region that was not apparent in the CeA or MeA.
This study is the first to link increases in anxiety like behaviour to structural changes within the basolateral amygdala in a model of prenatal ethanol exposure. While, the learning and memory deficits typically linked to prenatal alcohol exposure were not evident within this chronic low dose model this study has shown that exposure to even a relatively small amount of alcohol during development can lead to long term alterations in anxiety-like behaviour.