RGS2 drives male aggression in mice via the serotonergic system

Abstract

AbstractAggressive 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 inRgs2−/−mice, while anxiety is not affected. The aggressive behavior is directly correlated to the immediate early genec-fosinduction 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 Gi/oand Gq/11coupled 5HT and adrenergic receptors in serotonergic neurons ofRgs2-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.