Constitutive depletion of brain serotonin differentially affects rats’ social and cognitive abilities

Summary

Central serotonin appears a promising transdiagnostic marker of psychiatric disorders and a modulator of some of their key behavioral symptoms. In adult male Tph2 ^−/− rats, constitutively lacking central serotonin, we tested individual’s cognitive, social and non-social abilities and characterized group’s social organization under classical and ethological testing conditions. Using unsupervised machine learning, we identified the functions most dependent on serotonin. Although serotonin depletion did not affect cognitive performances in classical testing, in the home-cage it induced compulsive aggression and sexual behavior, hyperactive and hypervigilant stereotyped behavior, reduced self-care and exacerbated corticosterone levels. This profile recalled symptoms of impulse control and anxiety disorders. Serotonin appeared essential for behavioral adaptation to dynamic social environments. Our animal model challenges the essential role of serotonin in decision-making, flexibility, impulsivity, and risk-taking. These findings highlight the importance of studying everyday life functions within the dynamic social living environment to model complexity in animal models.

Graphical abstract

Highlights

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  Brain serotonin depletion did not impact cognitive abilities in classical procedures

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  Brain serotonin depletion compromised everyday behaviors in naturalistic home-cage

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  Most critical behaviors resembled symptoms of impulse control and anxiety disorders

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  Multidimensional testing and naturalistic conditions offered high translational value

Abstract

Biological sciences; Neuroscience; Behavioral neuroscience