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Screening for drugs to reduce zebrafish aggression identifies caffeine and sildenafil

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posted on 06.05.2020, 13:13 by Héctor Carreño Gutiérrez, Irene Vacca, Gido Schoenmacker, Madeleine Cleal, Anna Tochwin, Bethan O'connor, Andrew M. J. Young, Alejandro Arias Vasquez, Mathew J. Winter, Matthew O. Parker, William H. J. Norton
Although aggression is a common symptom of psychiatric disorders the drugs available to treat it are non-specific and can have unwanted side effects. In this study we have used a behavioural platform in a phenotypic screen to identify drugs that can reduce zebrafish aggression without affecting locomotion. In a three tier screen of ninety-four drugs we discovered that caffeine and sildenafil can selectively reduce aggression. Caffeine also decreased attention and increased impulsivity in the 5-choice serial reaction time task whereas sildenafil showed the opposite effect. Imaging studies revealed that both caffeine and sildenafil are active in the zebrafish brain, with prominent activation of the thalamus and cerebellum evident. They also interact with 5-HT neurotransmitter signalling. In summary, we have demonstrated that juvenile zebrafish are a suitable model to screen for novel drugs to reduce aggression, with the potential to uncover the neural circuits and signalling pathways that mediate such behavioural effects.

Funding

Seventh Framework Programme (FP7/2007–2013) under grant agreement no.602805

History

Citation

European Neuropsychopharmacology Volume 30, January 2020, Pages 17-29

Author affiliation

Department of Neuroscience, Psychology and Behaviour

Version

VoR (Version of Record)

Published in

European Neuropsychopharmacology

Volume

39

Pagination

17-29

Publisher

Elsevier for European College of Neuropsychopharmacology

issn

0924-977X

eissn

1873-7862

Acceptance date

10/10/2019

Copyright date

2019

Available date

01/11/2019

Publisher version

https://www.sciencedirect.com/science/article/pii/S0924977X1931716X

Language

en

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