Abstract

Anxiety and aggression are part of the behavioral repertoire of humans and animals. However, in their exaggerated form both can become maladaptive and result in psychiatric disorders. On the one hand, genetic predisposition has been shown to play a crucial modulatory role in anxiety and aggression. On the other hand, social experiences have been implicated in the modulation of these traits. However, so far, mainly experiences in early life phases have been considered crucial for shaping anxiety-like and aggressive behavior, while the phase of adolescence has largely been neglected. Therefore, the aim of the present study was to elucidate how levels of anxiety-like and aggressive behavior are shaped by social experiences during adolescence and serotonin transporter (5-HTT) genotype. For this purpose, male mice of a 5-HTT knockout mouse model including all three genotypes (wildtype, heterozygous and homozygous 5-HTT knockout mice) were either exposed to an adverse social situation or a beneficial social environment during adolescence. This was accomplished in a custom-made cage system where mice experiencing the adverse environment were repeatedly introduced to the territory of a dominant opponent but had the possibility to escape to a refuge cage. Mice encountering beneficial social conditions had free access to a female mating partner. Afterwards, anxiety-like and aggressive behavior was assessed in a battery of tests. Surprisingly, unfavorable conditions during adolescence led to a decrease in anxiety-like behavior and an increase in exploratory locomotion. Additionally, aggressive behavior was augmented in animals that experienced social adversity. Concerning genotype, homozygous 5-HTT knockout mice were more anxious and less aggressive than heterozygous 5-HTT knockout and wildtype mice. In summary, adolescence is clearly an important phase in which anxiety-like and aggressive behavior can be shaped. Furthermore, it seems that having to cope with challenge during adolescence instead of experiencing throughout beneficial social conditions leads to reduced levels of anxiety-like behavior.

Highlights

  • Anxiety and aggressiveness are essential traits to optimally cope with environmental challenges and trigger adaptive responses

  • Univariate analysis of variance (ANOVA) detected that body weight did not differ significantly between adverse social environment (AE) and beneficial social environment (BE) animals or between genotypes before the start of the experiment [week 0: social experience: F(1, 69) = 1.234, p = 0.271; genotype: F(2, 69) = 0.847, p = 0.433]

  • The present study clearly shows that adolescence is a phase where anxiety and aggressiveness can be shaped profoundly by social experiences

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Summary

Introduction

Anxiety and aggressiveness are essential traits to optimally cope with environmental challenges and trigger adaptive responses In their exaggerated form, i.e., if anxiety-like and aggressive behavior occur out of context and control, they are often associated with psychopathologies like generalized anxiety disorders, phobias, depression and antisocial personality disorder (Gross and Hen, 2004; Haller and Kruk, 2006). Both anxiety and aggressiveness can be shaped by environmental and genetic factors (Kendler, 1995; Hovatta and Barlow, 2008; Anholt and Mackay, 2012; Provençal et al, 2015). The social experiences during this life phase, for instance social instability or social subjugation, alter aggressive behavior in a number of rodent species (Wommack et al, 2003; Cumming et al, 2014; Hennessy et al, 2015)

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