RGS2 drives male aggression in mice via the serotonergic system

• Published in: Communications biology 2019-10, Vol.2 (1), p.373-373, Article 373
• Main Authors: Mark, Melanie D., Wollenweber, Patric, Gesk, Annika, Kösters, Katja, Batzke, Katharina, Janoschka, Claudia, Maejima, Takashi, Han, Jing, Deneris, Evan S., Herlitze, Stefan
• Format: Article
• Language: English
• Subjects: 13/1; 13/31; 13/44; 13/51; 14/19; 38/77; 38/90; 631/378/1457/3918; 64/60; 692/699/476/1300; 9/74; Action Potentials; Adrenergic receptors; Aggression; Aggression - physiology; Aggressive behavior; Aggressiveness; Animals; Anxiety; Anxiety - metabolism; Biology; Biomedical and Life Sciences; c-Fos protein; Calcium - metabolism; Cells, Cultured; Depression - metabolism; Dorsal Raphe Nucleus - metabolism; Hypothalamus (ventromedial); Life Sciences; Male; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Phenotypes; Proto-Oncogene Proteins c-fos - metabolism; Raphe nuclei; Receptors, Adrenergic - metabolism; Receptors, G-Protein-Coupled - metabolism; RGS Proteins - genetics; RGS Proteins - metabolism; RNA, Messenger - metabolism; Serotonergic Neurons - metabolism; Serotonin - metabolism; Serotonin receptors; Therapeutic applications; Ventromedial Hypothalamic Nucleus - metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-019-0622-0

Aggressive behavior in our modern, civilized society is often counterproductive and destructive. Identifying specific proteins involved in the disease can serve as therapeutic targets for treating aggression. Here, we found that overexpression of RGS2 in explicitly serotonergic neurons augments male aggression in control mice and rescues male aggression in Rgs2 −/− mice, while anxiety is not affected. The aggressive behavior is directly correlated to the immediate early gene c-fos induction in the dorsal raphe nuclei and ventrolateral part of the ventromedial nucleus hypothalamus, to an increase in spontaneous firing in serotonergic neurons and to a reduction in the modulatory action of G i/o and G q/11 coupled 5HT and adrenergic receptors in serotonergic neurons of Rgs2 -expressing mice. Collectively, these findings specifically identify that RGS2 expression in serotonergic neurons is sufficient to drive male aggression in mice and as a potential therapeutic target for treating aggression. Melanie Mark et al demonstrate that RGS2, a protein associated with stress disorders, drives male aggression through the serotonergic system. They show that exogenous expression of RGS2 in serotogenic neurons augments aggression in male mice and rescues the docile phenotype of Rgs2 knockouts but does not affect anxiety.