corticotropin-releasing factor-CRF, adrenocorticotropic hormone-ACTH, cortisol, noradrenaline serotonin, and neuropeptide Y). hypothalamus, amygdala, hippocampus, prefrontal cortex, locus coeruleus, raphe nucleus, pituitary gland, and adrenal gland) and associated neurochemical substrates (e.g. Studies of the effect of stress on behavior and physiology during the last century, conducted at cellular, molecular, physiological, and systems levels, have led to important knowledge on the brain and neuroendocrine structures involved (e.g.
At the physiological level, the effect of stressors is commonly assessed through measuring the level of cortisol (or corticosterone in rodents), the release of which is under control of the hypothalamo-pituitary-adrenocortical (HPA) stress axis. Zebrafish, a vertebrate genetic model developed in more recent years, also display a light/dark preference behavior: Adult zebrafish display scototaxis (or light avoidance), which is shown to be anxiety-related. Several classical behavioral assays, including the elevated plus-maze, the light/dark choice, and the open-field tests, have been used to measure anxiety-like behaviors in rodents, the animal models most widely used for stress research. The behaviors that are associated with stressors are often referred to as anxiety-related, manifesting as avoidance or aversion. Both acute and chronic stressors can lead to changes in behavior and physiology. At present, the word “stressor” is often used to refer to the stimulus (either external or internal) that perturbs homeostasis and thus exerts an undesirable effect on physiology or behavior, whereas “stress” is more broadly used to describe either the stimulus or the state of being in an undesirable situation. It was popularized by Hans Seyle through his books “The Stress of Life” and “Stress without Distress”. The word “stress” refers to external factors that disrupt homeostasis.
The findings that various stressors enhance while anxiolytics attenuate dark avoidance further reinforce that the light/dark preference behavior in larval zebrafish is fear/anxiety-associated. Those stimuli that elicit differential responses at behavioral and physiological levels warrant further studies at circuit levels to understand the underlying mechanisms.
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These results identify a series of stressors that can be easily administered to larval zebrafish. Surprisingly, using the cortisol assay, a physiological measure of stress, we uncover that all stimuli but heat and SI significantly increase the whole body cortisol levels. scotophobia), we find that heat, cold and UV stimuli significantly enhance their dark avoidance with heat having the most striking effect, whereas MD and SI have little influence on the behavior. Using a light/dark choice paradigm, in which larval zebrafish display an innate dark avoidance behavior (i.e. These stimuli are selected based on their perceived aversive nature to larval zebrafish. In this study, we have characterized the physiological and behavioral responses of larval zebrafish to several easily amenable stimuli, including heat, cold, UV, mechanical disturbance (MD), and social isolation (SI). Despite these attractive features, there is a scarcity of behavioral characterizations in larval zebrafish compared to other model organisms as well as adult zebrafish. Moreover, their small body size (~4–5 mm in length) is compatible with 96-well plates, making larval zebrafish amenable to high content screening. Larval zebrafish, with a simple and transparent vertebrate brain composed of ~100 K neurons, is well suited for deciphering entire neural circuit activity underlying behavior.
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