Embryonic alcohol exposure impairs associative learning performance in adult zebrafish

Abstract

The zebrafish has been proposed for modeling fetal alcohol spectrum disorders (FASD). Previous FASD research with zebrafish employed high concentrations of alcohol and/or long exposure periods. Here, we exposed zebrafish eggs to low doses of alcohol (0, 0.25, 0.50, 0.75 and 1.0% (vol/vol); external bath application of which 1/20th may reach the inside of the egg) at 16-h post-fertilization (hpf) and only for a short duration (2 h) in the hope to avoid gross morphological aberrations and to mimic the more frequent FASD exposure levels. Upon reaching adulthood the exposed and control zebrafish were tested for their associative learning performance in a plus-maze. Embryonic alcohol exposure led to no gross anatomical abnormalities and did not increase mortality. Unexposed (control) zebrafish showed excellent acquisition of association between a conditioned visual stimulus (CS) and food reward, demonstrated by their preference for the target zone of the maze that contained the CS during a probe trial in the absence of reward. However, alcohol-exposed fish showed no such preference and performed indistinguishable from random chance. Locomotor activity during training and the probe trial or the amount of food consumed during training did not differ between the embryonic alcohol exposed and unexposed (control) fish, suggesting that the impaired learning performance found was unlikely to be caused by altered motivation or motor function. Our results suggest that even very small amounts of alcohol reaching the embryo for only a short duration of time may have long lasting deleterious effects on cognitive function in vertebrates.

The zebrafish as a promising tool for modeling human brain disorders: A review based upon an IBNS Symposium

“…It is thus possible that although the dopaminergic neurons themselves may be intact, the development of their connectome is altered by embryonic alcohol exposure, and this alteration may explain the unresponsive nature of dopaminergic neurons to social stimuli. The intact nature of dopaminergic neurons and the possibility of abnormal ascending inputs to these neurons are also supported indirectly by finding unaltered motivation of embryonic alcohol exposed zebrafish to seek and obtain food in an associative learning task (Fernandes et al, 2014).…”

Fishing for Fetal Alcohol Spectrum Disorders: Zebrafish as a Model for Ethanol Teratogenesis

“…Individuals with FASD are known to have deficits in learning and memory 14 and zebrafish have been shown to recapitulate some of these deficits. 52,64,65 Associative learning in adult zebrafish has been shown to be impaired by a 2-h ethanol exposure starting at 16 hpf. 64 Carvan et al 52 found adult zebrafish that were exposed from 0 to 24 hpf to 0.06% and 0.18% ethanol took significantly more trial to predict the location of a food reward.…”

“…52,64,65 Associative learning in adult zebrafish has been shown to be impaired by a 2-h ethanol exposure starting at 16 hpf. 64 Carvan et al 52 found adult zebrafish that were exposed from 0 to 24 hpf to 0.06% and 0.18% ethanol took significantly more trial to predict the location of a food reward. However, Bailey et al 66 found that fish exposed to either 1% or 3% ethanol from either 8 to 10 hpf or 24 to 27 hpf did not have impaired spatial discrimination.…”

Pharmacological analyses of learning and memory in zebrafish (Danio rerio)

“…Fernandes et al, 2014; Bailey et al, 2015; and for a review see Cole et al, 2012 or Ali et al, 2011). However, the literature describing the acute effects of ethanol exposure during adolescence or adulthood on learning and memory in zebrafish is more modest.…”