Decynium-22 affects behavior in the zebrafish light/dark test

Decynium-22 (D-22) is an inhibitor of the uptake2 system of monoamine clearance, resulting in increased levels of dopamine and norepinephrine (and in some cases serotonin) in the nervous system and elsewhere. Uptake2 is mediated by low-affinity, high-capacity transporters that are inhibited by glucocorticoids, suggesting a mechanism of fast glucocorticoid-monoamine interaction in the brain and a possible target for antidepressants. D-22 dose-dependently increased anxiety-like behavior in adult zebrafish exposed to the light/dark test, monotonically increasing scototaxis (dark preference), but affecting risk assessment with an inverted-U-shaped response. These results suggest that the uptake2 system has a role in defensive behavior in zebrafish, presenting a novel mechanism by which stress and glucocorticoids could produce fast neurobehavioral adjustments in vertebrates.