The Effects of Binge Alcohol Consumption on the Developing Brain

Abstract

Exposure to ethanol during the third trimester brain growth spurt can have detrimental effects. Damage to the central nervous system being the most severe outcome resulting from prenatal ethanol exposure causing a range of deficits on a continuum of gross to subtle. Human data on the timing and dose of ethanol exposure that results in perturbation is limited, so the use of animal models in studying these precise effects is critical. This study aimed to investigate the effects of a double binge exposure to ethanol on post-natal day six (PN6) and post-natal day eight (PN8), in the third trimester equivalent of human brain development, using a rat model. The acute affects of ethanol exposure and withdrawal were assessed after the first binge on PN6. At weaning the animals were placed in a reversed light cycle housing environment and activity, anxiety, learning and memory experiments were conducted during the dark cycle, the period of normal activity for the rat. These experiments revealed a marked decrease in locomotion twenty-four and thirty-two hours following the first binge exposure on PN6, with severe seizure activity being greatest at twenty four hours post ethanol exposure. Habituation to an unfamiliar environment was not effected by ethanol exposure. Hyperactivity was observed in the open field and no difference in anxiety related behaviour was apparent following open-field testing. However, elevated T-maze testing revealed a difference in anxiety related behaviour. Ethanol exposed animals had a decreased learned fear response but no difference in innate fear. Learning and memory deficits were observed in novel object recognition testing and both the reference memory and working memory versions of the Morris water maze. Following behavioural testing, a pilot study was carried out to determine the number of synapses on the apical dendrites of the CA1 pyramidal cells was using the physical disector method on electron micrographs. There was a significant decrease in synapses per unit volume in the ethanol treated animals compared to controls. This study provides an important link between structural changes and functional deficits associated with a double binge-like ethanol exposure during the third trimester brain growth spurt.