Life-threatening, high-intensity trauma- and context-dependent anxiety in zebrafish and its modulation by epinephrine

Trauma-related psychopathology transpires in some individuals after exposure to a life-threatening event. While aberrant adrenergic processes may contribute to this, a clear understanding of how said processes influence trauma-related conditions, remain inadequate. Here, we aimed to develop and describe a novel zebrafish (Danio rerio) model of life-threatening trauma-induced anxiety that may be representative of trauma related anxiety, and to evaluate the impact of stress-paired epinephrine (EPI) exposure in the model system. Four groups of zebrafish were each exposed to different and unique stress-related paradigms, i.e., i) a sham (trauma free), ii) high-intensity trauma (triple hit; THIT), iii) high-intensity trauma in the presence of EPI exposure (EHIT), and iv) EPI exposure on its own, all applied in the presence of a color context. Novel tank anxiety was subsequently assessed at 1, 4, 7 and 14 days after the traumatic event. The present results demonstrate that 1) through day 14, THIT or EPI exposure alone induced persistent anxiety-like behavior, 2) EHIT blunted the delayed anxiety-like sequalae associated with severe trauma, 3) exposure to a trauma-paired color context prior to anxiety testing bolstered the subsequent anxiety-like behavior of THIT, but not EHIT -exposed fish, and 4) despite this, THIT- and EPI-exposed fish showed a lesser degree of contextual avoidance behavior compared to sham- or EHIT-exposed fish. These results indicate that the stressors induced long-lasting anxiety-like behavior reminiscent of post trauma anxiety, while EPI displays complex interactions with the stressor, including a buffering effect to subsequent exposure of a trauma-paired cue.