Effects of acute and chronic ethanol exposure on the behavior of adult zebrafish (Danio rerio)

Abstract

The zebrafish has been a popular subject of embryology and genetic research for the past three decades. Recently, however, the interest in its neurobiology and behavior has also increased. Nevertheless, compared to other model organisms, e.g., rodents, zebrafish behavior is understudied and very few behavioral paradigms exist for mutation or drug screening purposes. Alcoholism is one of the biggest and costliest diseases whose mechanisms are not well understood. Model organisms such as the zebrafish may be utilized in this line of research. Previously, we investigated the effects of acute ethanol exposure on adult zebrafish using four behavioral paradigms and employing manual quantification methods. Here, we study the effects of chronic ethanol exposure and analyze how it modifies the effects of acute ethanol treatment. We employ a videotracking-based automated quantification method in a predator model paradigm and show that this method is capable of detecting an avoidance reaction that is ameliorated by higher doses of ethanol, a potential anxiolytic effect. Importantly, we also demonstrate that chronic, two week long, exposure to ethanol results in significant adaptation to this substance in adult zebrafish. Overall, our results suggest that zebrafish will be an appropriate subject for high throughput screening applications aimed at the analysis of the mechanisms and pharmacology of acute and chronic ethanol induced changes in the vertebrate brain.

Effect of novelty stress on behavioral responses of Danio rerio and assessment of dose-dependent effects of anxiolytics of benzodiazepine structure with phenazepam as an example

“…Исследования поведения Danio rerio (zebrafish) применяются главным образом в нейробиоло-гии [15,22], нейроэтологии [4,16,17] и нейрофар-макологии [6,14,19]. Активное плавание, адаптация к новой обстановке, короткий репродуктивный пери-од, высокая плодовитость и низкая себестоимость дают возможность использовать Danio rerio в каче-стве животных моделей для лабораторных иссле-дований [25].…”

In vitroandin vivomodels of acute alcohol exposure

“…Thus, optimal AAA models should fulfill several criteria: (1) Define the length of alcohol exposure. In vitro the length of acute alcohol treatment is variable in diverse published experimental settings and range from seconds to hours; it is currently accepted that treatment with alcohol for up to 24 h is considered as an acute setting [98][99][100][101][102][103][104][105][106] . In vivo the consumption of alcohol in one setting implies that the entire dose of alcohol is consumed at once, while a 'binge' is defined by NIAAA as an excessive pattern of alcohol drinking that produces BAL greater than 0.08% within a 2-h period and may, or may not, be associated with dependence [11,12,17,18] .…”

“…(2) Establish an exposure to an accurate concentration of ethanol. For in vitro studies the 10-100 mmol/L ethanol range is considered physiological, with 25 mmol/L ethanol being close to 0.08% BAL achieved in vivo after 4-5 drink equivalents [7,11,12,[98][99][100][101][102][103][104][105][106] . For the in vivo studies an 0.08% BAL or above this level yields signs of intoxication and it is employed in the majority of biomedical studies [107][108][109][110][111][112][113][114][115][116][117][118][119][120][121] .…”

“…Currently there are human and non-human models of AAA, and the later include use of invertebrates [146][147] and ver tebrates [21,25,37,44,46,47,53,65,72,86,93,94,98,104,110,111] . The invertebrate models (Drosophila melanogaster [146,147] , Caenorhabditis elegans [105] ) and those using lower vertebrates (Zebra fish Danio rerio) [98] are invaluable for research of the effect of alcohol on behavior, development and maintenance of memory, and on basic signaling mechanisms. These models offer the advantage of a well-defined genetic background, high-turnover rate of experiments due to short life cycle and relatively low-cost; in light of these advantages they constitute an excellent resource for research of signaling pathways and are highly desirable for their drug-screening capacity.…”

A Novel Method of Drug Administration to Multiple Zebrafish (<em>Danio rerio</em>) and the Quantification of Withdrawal

“…Previously used methods were practical, however, we sought to develop a method that reduced netting, with its associated time costs, and allowed simultaneous, precisely timed administration of the drug of interest to large numbers of fish. In traditional research using ethanol, zebrafish are netted and transferred from one tank to another containing the appropriate mixture of ethanol and water [10][11][12] . While this method is widely accepted, netting zebrafish may increase the variability in the time taken to introduce and remove the fish from the drug solution.…”