Ethanol affects behavior and HPA axis activity during development in zebrafish larvae

Abstract

Recent studies have shown that long-term alcohol intake from food can lead to numerous mental disorders in humans, and the social and health effects of excessive intake of alcohol currently represent serious problems for governments and families worldwide. However, to date, it has not been determined how alcohol affects the hypothalamic–pituitary–adrenal (HPA) axis. The zebrafish offers a good model for studying the toxicology of food-grade ethanol. In the present study, using zebrafish larvae exposed to 1% ethanol, we performed zebrafish behavioral analysis. Samples were collected for enzyme-linked immunosorbent assay (ELISA) and quantitative real time-polymerase chain reaction (qRT-PCR) experiments, and statistical analysis was performed. We found that ethanol decreased the locomotor activity of zebrafish larvae, which showed a more intense reaction to external stimuli. Ethanol also increased the level of HPA axis hormones in zebrafish larvae, influenced the level of neurotransmitters, and altered the expression of key genes in neurotransmitter metabolism. Ethanol exposure affects zebrafish behavior, increases the level of HPA axis hormones in zebrafish larvae, affects the level of neurotransmitters, and affects the expression of key genes in dopamine and serotonin metabolism. These findings may help to elucidate the effects of ethanol on HPA axis activity.

The importance of individual variation for the interpretation of behavioural studies: ethanol effects vary with basal activity level in zebrafish larvae

“…Zebrafish larvae in early stages of development (5-8 dpf) exhibit similar concentration-dependent behavioural responsiveness as adult zebrafish in terms of activity level (Lockwood et al 2004;Ikeda et al 2013;Puttonen et al 2013). The general pattern of impact is relatively consistent among studies, despite some variation in the exact concentrations applied (Guo et al 2015;Tran et al 2016a;Du et al 2020). A concentration of 0.5% alcohol typically has a stimulating effect, with elevated swimming velocity and erratic swimming patterns, while 1.0% alcohol has an opposite, sedative effect, as also confirmed in a recent study by Tsang et al (2019).…”

“…The majority of research, using animal models to understand and treat human alcoholism, has historically exploited rats and mice (Bennett et al 2006;Bell et al 2017). However, zebrafish have also been discovered as suitable system in this field to study alcohol-related toxicology and addiction (Gerlai et al 2000;Echevarria et al 2011), including investigations into alcohol tolerance, sensitization, and withdrawal (Cachat et al 2010;Tran and Gerlai 2014;Tran et al 2015), and individual variation in and chronic exposure effects on stress response mechanisms (Wong et al 2019;Goodman and Wong 2020;Du et al 2020).…”

“…The up-and downregulation are associated with the gradual and steady rise in ethanol uptake into the brain over time (Gerlai et al 2009;Rosemberg et al 2012;Tran et al 2015;Guo et al 2015). Various interactive mechanisms have been proposed to play a role in explaining these effects, including an effect on functioning of the HPI axis (Du et al 2020) and on GABA A receptor expression (Goodman and Wong 2020).…”

Neu1 deficiency induces abnormal emotional behavior in zebrafish

“…Moreover, Neu1-KO zebrafish exhibited a drastic alteration in the expression of emotional genes, especially in the HPA axis. In general, a decreased HPA axis has been considered as a low anxiety condition in zebrafish 39 . In addition, we noted that Neu1-KO zebrafish showed high interaction with the "unfamiliar" opponent in the mirror.…”

Cardiotoxicity of Zebrafish Induced by 6-Benzylaminopurine Exposure and Its Mechanism

“…Specifically, the hypothalamus secretes corticotropin-releasing hormone (CRH), which in turn acts on the pituitary to release adrenocorticotropic hormone (ACTH). ACTH then acts on the adrenal gland to secrete glucocorticoid (GC), which modulates HPA axis activity through the glucocorticoid receptor (GR or nr3c1) [ 6 ]. The HPA axis is an important aspect of the neuroendocrine system because it controls stress responses and regulates many physical activities.…”