Long-term behavioral impairment following acute embryonic ethanol exposure in zebrafish

Abstract

BACKGROUND Developmental exposure to ethanol has long been known to cause persisting neurobehavioral impairment. However, the neural and behavioral mechanisms underlying these deficits and the importance of exposure timing are not well-characterized. Given the importance of timing and sequence in neurodevelopment it would be expected that alcohol intoxication at different developmental periods would result in distinct neurobehavioral consequences. METHODS Zebrafish embryos were exposed to ethanol (0%, 1%, 3%) at either 8-10 or 24-27 hours post-fertilization (hpf) then reared to adolescence and evaluated on several behavioral endpoints. Habituation to a repeated environmental stimulus and overall sensorimotor function were assessed using a tap startle test; measurements of anxiety and exploration behavior were made following introduction to a novel tank; and spatial discrimination learning was assessed using aversive control in a three-chambered apparatus. Overt signs of dysmorphogenesis were also scored (i.e. craniofacial malformations, including eye diameter and midbrain-hindbrain boundary morphology). RESULTS Ethanol treated fish were more active both at baseline and following a tap stimulus compared to the control fish and were hyperactive when placed in a novel tank. These effects were more prominent following exposure at 24-27 hpf than with the earlier exposure window, for both dose groups. Increases in physical malformation were only present in the 3% ethanol group; all malformed fish were excluded from behavioral testing. DISCUSSION These results suggest specific domains of behavior are affected following ethanol exposure, with some but not all of the tests revealing significant impairment. The behavioral phenotypes following distinct exposure windows described here can be used to help link cellular and molecular mechanisms of developmental ethanol exposure to functional neurobehavioral effects.

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

“…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. Taken together, these results demonstrate that not only can zebrafish be used to model the learning impairments of FASD but also to show the variability of embryonic ethanol exposure.…”

“…60,66,67 Parker et al 60 reported that exposure to 0.12% ethanol from 48 to 216 hpf caused adult zebrafish to spend significantly more time at the bottom of the tank compared to untreated controls. This behavior is interpreted as elevated anxiety.…”

“…However, spending too much time at the top of the water column can also be interpreted as a maladaptive behavior. 66,68 Exposure to 3% ethanol between 24 to 27 hpf leads to a significant time spent in the top of the tank, suggesting the acquisition of maladaptive behaviors. 66 The exposure regimens across these studies differ substantially, suggesting that the timing, duration and length of exposure may contribute to the variability in behavioral outcomes.…”

Zebrafish Models of Human Disease: Gaining Insight into Human Disease at ZFIN

“…Zebrafish embryos exposed to ethanol have been used as models of fetal alcohol spectrum disorders, which result from maternal alcohol consumption during pregnancy (Table 1C). Zebrafish fetal alcohol spectrum disorders models have been used to understand the effects of prenatal alcohol exposure on behavior (Bailey et al 2015; Fernandes et al 2015), to gain an understanding of affected signaling pathways (Pappalardo-Carter et al 2013; C Zhang et al 2014; Zhang et al 2015), and to understand associated retinal tissue defects (Muralidharan et al 2014). Zebrafish have also been used to understand human obesity, which can have its cause rooted in multiple factors, including genetics and lifestyle.…”

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.…”