Masters Thesis

A larval zebrafish model of glucocorticoid-serotonin interactions in behavioral stress reactivity

Neural mechanisms of stress are highly conserved across animals. Glucocorticoids (such as cortisol in humans) and serotonin are two neural signaling molecules that are essential to normal stress reactivity in many animals. These chemical signaling molecules are also believed to interact during stress responses. The details and functional consequences of that interaction are not well understood, but they have been proposed to influence the development of stress related disorders such as depression and anxiety in humans, as well as responses to antidepressant medications. This study used a mutant zebrafish strain, s357gr-/-, in which the glucocorticoid receptor is non-functional, to investigate the roles that glucocorticoids, serotonin, and their interactions play in behavioral stress reactivity. This mutant line has been proposed to be a model of behavioral stress disorders in humans. Mutant larvae showed larger locomotor responses and less habituation in an auditory-evoked startle test compared to wildtype sibling controls, despite having lower spontaneous locomotor activity levels. Mutants also had elevated whole cortisol levels. Fluoxetine was shown to increase spontaneous swimming activity in mutants as well as reduce locomotor activity in response to the auditory stimulus. These results provide partial support for the s357gr-/- zebrafish mutant as a model of human stress disorders in which the primary cause is a disruption in glucocorticoid signaling.