Bully or Bullied? The Zebrafish as a Model for Social Stress and Depression

Detta är en avhandling från Uppsala : Acta Universitatis Upsaliensis

Sammanfattning: The zebrafish is evaluated as a model for social stress, depression and anxiety. I conclude that it is suitable, especially for studies of sex differences. In humans, women are more prone to depression but most animal studies are performed in males. A popular way to study depression is by means of social stress, which is often a contributing factor to depression. However, social stress in female rodents is difficult to study since female aggression is mostly limited to maternal defence. Thus, there is a need for models to study depression and anxiety in females, as well as sex differences in these disorders.As personality is a risk factor for developing depression, I aimed at exploring correlated behaviours that together characterise personalities. My work confirmed that zebrafish, as numerous other species, show strong correlations between boldness and aggression on the one hand, and neurobiological reactions to social stress on the other. In general, males were bolder than females, but there were no differences in aggressive behaviours between the sexes. It was also confirmed that both acute and chronic social stress activates the dopamine and serotonin systems in the brain, and that subordinate individuals appear to be more stressed, based on serotonergic activity.Further, I studied the consequences of altered levels of serotonin during development, such as would be the case when antidepressants are used during pregnancy. Zebrafish embryos were treated with drugs that affect the serotonin system by increasing or decreasing serotonin levels. Depletion of serotonin increased the expression of several serotonin-related genes but had no effect on morphology. In contrast, increasing serotonin levels only showed small effects on gene expression, but increased the length of the myotomes in the spinal cord. Together with other studies, my results indicate that fluvoxamine might be a suitable choice for treatment of depression during pregnancy.In conclusion, my results show that the zebrafish is a valid model organism for studying social stress, depression and anxiety disorders and it should therefore be considered when developing new animal models for depression. It will especially be beneficial in studies of sex differences.