Mild Embryonic Ethanol Exposure Induced Selective Dopaminergic Neurotransmission-Related Changes in Zebrafish: A Review and a Working Hypothesis.

Abstract

Fetal alcohol spectrum disorders (FASD) result from exposure to alcohol (ethanol) during embryonic development. These diseases cause lifelong struggle for the affected patients. Due to the complex nature of how alcohol affects embryonic development, understanding of underlying mechanisms is lacking and treatment options are limited. Reliable diagnostic markers are also unavailable. As a start to bridge this hiatus, animal models have been proposed. One of the most recent ones among these animal models is the zebrafish. In this review, I focus on our own efforts that attempted to model the milder and most prevalent end of the spectrum of this disorder using zebrafish. We discovered that a short period (2 h-long) exposure of the zebrafish embryo to low doses of alcohol (up to 1% vol/vol external bath) at 24th hour post-fertilization led to a lifelong and dose-dependent impairment of social behavior (shoaling) in zebrafish, associated with an apparently selective disruption of dopaminergic neurotransmitter system responses. Here I review these findings and, for example, discuss how analysis of the neurochemistry of the zebrafish brain may aid our understanding of the mechanisms underlying embryonic alcohol-induced abnormalities. I theorize about how a non-selective and pharmacologically complex drug like alcohol may lead to the apparently selective impairment in shoaling and dopaminergic responses in zebrafish. Last, I briefly delineate future plans that may address questions including what specific brain areas, synaptic and molecular mechanisms may underlie the behavioral and neurochemical effects of embryonic alcohol exposure we have observed in zebrafish.