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Updated: Jan 25, 2026

The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress
Published on: July 4, 2013
Enhanced aggressive phenotype of Tph2 knockout rats is associated with diminished 5-HT1A receptor sensitivity
Deborah G A Peeters1, Sietse F de Boer2, Anneke Terneusen3
1Dept of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands; Dept of Psychiatry, Radboud University Medical Centre, Nijmegen, the Netherlands.
Abstract:
Brain serotonin (5-HT) plays a key role in aggressive behaviours and related psychopathologies, but its precise mechanism of action remains elusive. Genetic animal models may provide a tool to elucidate the relationship between aggression and serotonin. The present study showed that tryptophan hydroxylase 2 (Tph2) knockout (KO) rats, which exhibit profoundly diminished extracellular serotonin levels, display increased aggressiveness compared to their Tph2 wildtype (WT) counterparts. However, the level of aggression in Tph2 KO rats did not equal that of feral wild type Groningen (WTG) rats. To investigate whether enhanced 5-HT1A receptor functionality may be present in Tph2 KO rats, we tested the acute anti-aggressive potency of the highly selective 5-HT1A receptor full agonist NLX-112 (a.k.a. befiradol or F13640). Data show that compared to Tph2 WT and WTG rats, the NLX-112 dose-effect curve was shifted to the right in Tph2 KO animals. These results suggest that, unlike previous reports in Tph2 KO mice, Tph2 KO rats have a decreased 5-HT1A receptor sensitivity compared to both Tph2 WT and WTG animals.
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