The Use of Docosahexaenoic Acid Supplementation to Ameliorate the Hyperactivity of Rat Pups Induced by in utero Ethanol Exposure

ABSTRACT

It has been demonstrated that in utero ethanol(EtOH) exposure induces hyperactive behavior and learning disturbances in offspring. In order to investigate the effects of docosahexaenoic acid(DHA) on these neurobehavioral dysfunctions of rat pups induced by in utero EtOH exposure, pregnant Wistar rats were divided into four treatment groups depending on the type of oil added to the diet and drinking water as follows; (a)5% safflower oil with tap water(TW/n−6), (b)3% safflower oil and 2% DHA with tap water(TW/n−3), (c)5% safflower oil with 10%−EtOH(ET/n−6), (d)3% safflower oil and 2% DHA with 10%−EtOH(ET/n−3) at gestational day (GD)7. 10%−EtOH was administered to dams in ET/n−6 and ET/n−3 groups from GD 7 to the pups’ weaning(postnatal week 4), and all pups were fed with the same diet that was given to their dams during the entire examination period. The open−field test and the water E−maze test were conducted for all pups, and a spontaneous motor activity test and the Sidman electric shock avoidance test were performed for some of male pups. Amounts of monoamine metabolites in striatum were then determined, and fatty acid analyses of total brain lipids were performed. The male pups in the ET/n−6 group showed significantly more rearing and square−crossing movements in the open−field test, and significanrly higher spontaneous motor activity during the dark period in the daily cycle compared to the males in the TW/n−6 group. The male pups in the ET/n−3 group showed fewer of these behaviors in the open−field test compared to the ET/n−6 group males, and a normal pattern of spontaneous motor activity. Learning disturbance induced by in utero EtOH exposure was not observed in the E−shaped water maze, but was observed in the avoidance rates in the Sidman electric shock avoidance test. However, there was no significant modifying effect of DHA on the avoidance rates in EtOH exposed pups. The analysis of the fatty acid composition of total lipids in the brains of the pups revealed high levels of DHA in the diet reflected an increased level of brain DHA and caused a decreased level of the brain arachidonic acid. Retroconversion from DHA to eicosapentaenoic acid was also observed. However, there was no significant effect of DHA on the levels of monoamine metabolites. These results support the hypothesis that DHA can counteract the attention deficit hyperactivity disorder.