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Aggression and monoamines: Effects of sex and social rank in zebrafish (Danio rerio)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology. (Svante Winberg)
Sveriges lantbruksuniversitet, Institutionen för vilt, fisk och miljö .
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
2012 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 228, no 2, 333-338 p.Article in journal (Refereed) Published
Abstract [en]

Social defeat is a common model for studies on depression. However, such models are most often used to study aggression in males and sex differences in depression may therefore be overseen. This study investigated the potential of the zebrafish (Danio rerio) as a model for male and female aggression. In addition, effects on the brain serotonergic and dopaminergic neurotransmitter systems after agonistic interaction are well studied in many species, but not in zebrafish. We wanted to explore whether the zebrafish follows the same patterns as many other species. Therefore, the effects of agonistic interaction on brain monoaminergic activity were studied in adult male and female wild-type zebrafish. The fish interacted in pairs with one of the same sex for five days during which agonistic behaviour was quantified daily. Clear dominant/subordinate relationships developed in all pairs, both in males and females. The frequency of aggressive acts increased over time but did not differ between male and female pairs. Further, we found that dyadic agonistic interaction resulted in elevated brain serotonergic activity in subordinate zebrafish, as indicated by elevated hindbrain 5-hydroxyindoleacetic acid to serotonin ratios (5-hydroxyindolacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratios). We also observed a sex difference in forebrain dopamine levels and forebrain 5-HIAA/5-HT ratios, with females displaying higher concentrations of dopamine but lower 5-HIAA/5-HT ratios than males. These results suggest that zebrafish is a suitable model for studies on female aggression and sex differences in brain monoaminergic neurotransmission.

Place, publisher, year, edition, pages
2012. Vol. 228, no 2, 333-338 p.
Keyword [en]
Dominance, Aggression, Zebrafish, Monoamine, Sex difference
National Category
URN: urn:nbn:se:uu:diva-168935DOI: 10.1016/j.bbr.2011.12.011ISI: 000301318900012OAI: oai:DiVA.org:uu-168935DiVA: diva2:504290
Available from: 2012-02-20 Created: 2012-02-20 Last updated: 2014-01-22Bibliographically approved
In thesis
1. Bully or Bullied?: The Zebrafish as a Model for Social Stress and Depression
Open this publication in new window or tab >>Bully or Bullied?: The Zebrafish as a Model for Social Stress and Depression
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 66 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 926
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Research subject
urn:nbn:se:uu:diva-205425 (URN)978-91-554-8725-6 (ISBN)
Public defence
2013-10-02, B21, Biomedicinskt Centrum, Husargatan 3, Uppsala, 09:15 (English)
Available from: 2013-09-11 Created: 2013-08-16 Last updated: 2014-01-22

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