Investigating the onset of behavioral effects of alcohol intake during zebrafish early development

Abstract

Alcohol is a legal drug of great social acceptance and the impacts of its excessive consumption are targets of concern in the last decades. One of the main damages associated with the use of alcoholic beverages is its consumption by pregnant women. Exposure to alcohol during the prenatal phase compromises the function of the placenta and the fetus development, which can lead to fetal alcohol spectrum disorders (FASD), responsible for morphological, sensory, and cognitive abnormalities. Many studies have sought to identify the mechanisms of action of this substance at the cellular level and, due to limitations in studies with humans, many research use alternative animal models, such as the zebrafish (Danio rerio). Although recent research has explored this vertebrate as a model for alcoholic exposure during development, these studies are mainly focused on embryonic morphological malformations, with a gap in the knowledge of possible behavioral and cognitive deficits in individuals who do not have visible physical deformities. Thus, this thesis aimed to investigate whether early exposure to moderate doses of alcohol can cause behavioral or cognitive alterations, and especially, whether these signals would be detected at early stages of life. For this, we (1) characterized the embryonic development of zebrafish under differents alcohol concentrations; (2) investigated behavioral changes in zebrafish larvae under the context of a novel tank and inhibitory avoidance; (3) analyzed behavioral and neuronal effects of alcohol exposure at different embryonic stages memory, examining the levels of cell death at each stage; and (4) evaluated the effects of embryonic alcohol exposure on place preference, in fry and adult zebrafish. Although in our studies we used only doses considered low or moderate, we found changes in development in various behavioral contexts. Our results showed that in addition to the alcohol concentration used and the embryonic stage in which animals were exposed, the effect of alcohol also depends on the particular behavior that is being observed, requiring multidisciplinary analyzes. We observed that behavioral indicators of FASD can be detected at very early ages and could be useful to the precoce diagnosis of the disorder. Also, we confirm the versatility of zebrafish as an animal model for studies of behavior and pharmacology, and especially of development, since this model facilitated scientific approaches that would be more difficult to be developed in mammalian models.