TPH2 knockout rats cannot accept social defeat in resident-intruder test

Brain serotonin (5-HT) is one of the key regulators of aggressive behavior and social defeat stress mechanisms. We had previously found that abolishing central 5-HT biosynthesis increases aggression, as tryptophan hydroxylase 2 (Tph2-/-) knockout rats (TPH2-KO) are more aggressive than wild-type (WT) counterparts. In this elaboration, we compared different types of intruders to expand our understanding of the aggressive phenotype in TPH2-KO rats. The resident-intruder paradigm was applied to evaluate the territorial aggression of rats, where isolated residents (TPH2-KO, WT male, 36 weeks, n=9), were presented with socialized intruders, either 50% smaller (S-I) or 30% larger by weight (L-I). The behavioral profile of TPH-2-KO rats was similar to WT with respect to the S-I group, but showed significantly more aggression when presented with the larger animals of the L-I group. Compared to WT, the TPH-2-KO initiated their attacks sooner (p = 0. 0001), fought for longer periods (p = 0. 0002), and spent less time in non-social exploration (p = 0.0014). Residents from both the WT and TPH-2-KO groups tended to cease their attacks upon the submission of smaller animals. However, while WT residents behave similarly with the L-I intruders, the TPH-2-KO spent much more time attacking the larger animals. These results demonstrate that highly aggressive behavior in TPH2-KO rats can be associated not with a depressive-like state caused by lack of 5-HT, but with a strong motivation towards advancing in the social dominance hierarchy. This work was supported by the project ID:95444211 of the St.Petersburg State University, St.Petersburg, Russia.