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Bully or Bullied?: The Zebrafish as a Model for Social Stress and Depression
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
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
National Category
Research subject
URN: urn:nbn:se:uu:diva-205425ISBN: 978-91-554-8725-6OAI: oai:DiVA.org:uu-205425DiVA: diva2:641407
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
List of papers
1. Boldness predicts social status in zebrafish (Danio rerio)
Open this publication in new window or tab >>Boldness predicts social status in zebrafish (Danio rerio)
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2011 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 6, no 8, e23565Article in journal (Refereed) Published
Abstract [en]

This study explored if boldness could be used to predict social status. First, boldness was assessed by monitoring individual zebrafish behaviour in (1) an unfamiliar barren environment with no shelter (open field), (2) the same environment when a roof was introduced as a shelter, and (3) when the roof was removed and an unfamiliar object (Lego® brick) was introduced. Next, after a resting period of minimum one week, social status of the fish was determined in a dyadic contest and dominant/subordinate individuals were determined as the winner/loser of two consecutive contests. Multivariate data analyses showed that males were bolder than females and that the behaviours expressed by the fish during the boldness tests could be used to predict which fish would later become dominant and subordinate in the ensuing dyadic contest. We conclude that bold behaviour is positively correlated to dominance in zebrafish and that boldness is not solely a consequence of social dominance.

National Category
Natural Sciences
urn:nbn:se:uu:diva-157531 (URN)10.1371/journal.pone.0023565 (DOI)000294121300060 ()
Available from: 2011-08-22 Created: 2011-08-22 Last updated: 2015-07-24Bibliographically approved
2. Aggression and monoamines: Effects of sex and social rank in zebrafish (Danio rerio)
Open this publication in new window or tab >>Aggression and monoamines: Effects of sex and social rank in zebrafish (Danio rerio)
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.

Dominance, Aggression, Zebrafish, Monoamine, Sex difference
National Category
urn:nbn:se:uu:diva-168935 (URN)10.1016/j.bbr.2011.12.011 (DOI)000301318900012 ()
Available from: 2012-02-20 Created: 2012-02-20 Last updated: 2014-01-22Bibliographically approved
3. Social modulation of brain monoamine levels in zebrafish
Open this publication in new window or tab >>Social modulation of brain monoamine levels in zebrafish
2013 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 253, 17-24 p.Article in journal (Refereed) Published
Abstract [en]

In social species animals tend to adjust their social behaviour according to the available social information in the group, in order to optimize and improve their one social status. This changing environment requires for rapid and transient behavioural changes that relies primarily on biochemical switching of existing neural networks. Monoamines and neuropeptides are the two major candidates to mediate these changes in brain states underlying socially behavioural flexibility. In the current study we used zebrafish (Danio rerio) males to study the effects of acute social interactions on rapid regional changes in brain levels of monoamines (serotonin and dopamine). A behavioural paradigm under which male zebrafish consistently express fighting behaviour was used to investigate the effects of different social experiences: winning the interaction, losing the interaction, or fighting an unsolved interaction (mirror image). We found that serotonergic activity is significantly higher in the telencephalon of winners and in the optic tectum of losers, and no significant changes were observed in mirror fighters suggesting that serotonergic activity is differentially regulated in different brain regions by social interactions. Dopaminergic activity it was also significantly higher in the telencephalon of winners which may be representative of social reward. Together our data suggests that acute social interactions elicit rapid and differential changes in serotonergic and dopaminergic activity across different brain regions.

National Category
Behavioral Sciences Biology
urn:nbn:se:uu:diva-205419 (URN)10.1016/j.bbr.2013.07.012 (DOI)000324720500003 ()23850359 (PubMedID)
Available from: 2013-08-16 Created: 2013-08-16 Last updated: 2014-01-22Bibliographically approved
4. Effects of drugs that alter serotonin levels on morphology and expression of genes related to serotonin signalling
Open this publication in new window or tab >>Effects of drugs that alter serotonin levels on morphology and expression of genes related to serotonin signalling
(English)Manuscript (preprint) (Other academic)
National Category
urn:nbn:se:uu:diva-205421 (URN)
Available from: 2013-08-16 Created: 2013-08-16 Last updated: 2014-01-22

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