Abstract
Zebrafish is a model organism that is receiving considerable attention in preclinical research. Particularly important is the use of zebrafish in behavioral pharmacology, where a number of high-throughput experimental paradigms have been proposed to quantify the effect of psychoactive substances consequences on individual and social behavior. In an effort to assist experimental research and improve animal welfare, we propose a mathematical model for the social behavior of groups of zebrafish swimming in a shallow water tank in response to the administration of psychoactive compounds to select individuals. We specialize the mathematical model to caffeine, a popular anxiogenic compound. Each fish is assigned to a Markov chain that describes transitions between freezing and swimming. When swimming, zebrafish locomotion is modeled as a pair of coupled stochastic differential equations, describing the time evolution of the turn-rate and speed in response to caffeine administration. Comparison with experimental results demonstrates the accuracy of the model and its potential use in the design of in-silico experiments.
Highlights
Animal experiments are a standard practice for hypothesis testing in preclinical research [1,2]
We conducted in-silico experiments to demonstrate the predictive power of the model in anticipating experimental results on schooling and shoaling
We registered a dependence on the social environment with respect to pSF (F1,50 5.416, p 0.027), we did not detect any variation in post-hoc analysis
Summary
Animal experiments are a standard practice for hypothesis testing in preclinical research [1,2]. Zebrafish (Danio rerio) has emerged as a species of choice in experimental studies in pharmacology where it is used in high throughput drug screening of several psychoactive compounds [7,8]. Zebrafish experiments could clarify some of the open questions on anxiety-related behaviors in humans [10]. In these experiments, fish behavior is monitored in an experimental setup to investigate how anxiety-related behavior is modulated by anxiolytic and anxiogenic compounds, such as caffeine, cocaine, and ethanol [11,12,13,14,15]. Experiments on fish treated with such compounds have revealed numerous anxiety-related behaviors, including erratic activity
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