Social behaviors are among the most important motivated behaviors. How dopamine (DA), a “reward” signal, releases during social behaviors has been a topic of interest for decades. Here, we use a genetically encoded DA sensor, GRAB_DA2m, to record DA activity in the nucleus accumbens (NAc) core during various social behaviors in male and female mice. We find that DA releases during approach, investigation and consummation phases of social behaviors signal animals’ motivation, familiarity of the social target, and valence of the experience, respectively. Positive and negative social experiences evoke opposite DA patterns. Furthermore, DA releases during mating and fighting are sexually dimorphic with a higher level in males than in females. At the functional level, increasing DA in NAc enhances social interest toward a familiar conspecific and alleviates defeat-induced social avoidance. Altogether, our results reveal complex information encoded by NAc DA activity during social behaviors and their multistage functional roles.

The monoamine neuromodulator dopamine (DA) plays a critical role in the brain, and the ability to directly measure dopaminergic activity is essential for understanding its physiological functions. We therefore developed the first red fluorescent GPCR-activation–based DA (GRAB _DA ) sensors and optimized versions of green fluorescent GRAB _DA sensors following our previous studies. In response to extracellular DA, both the red and green GRAB _DA sensors have a large increase in fluorescence (ΔF/F ₀ values of 150% and 340%, respectively), with subcellular resolution, subsecond kinetics, and nanomolar to submicromolar affinity. Moreover, both the red and green GRAB _DA sensors readily resolve evoked DA release in mouse brain slices, detect compartmental DA release in live flies with single-cell resolution, and report optogenetically elicited nigrostriatal DA release as well as mesoaccumbens dopaminergic activity during sexual behavior in freely behaving mice. Importantly, co-expressing red GRAB _DA with either green GRAB _DA or the calcium indicator GCaMP6s provides a robust tool for simultaneously tracking neuronal activity and dopaminergic signaling in distinct circuits in vivo .

Rationale: Aggression is an innate social behavior prevalent across animal species. However, in modern human society, inter-personal aggression is considered disruptive and detrimental to both families and communities. Clinically, antipsychotics, which primarily target dopamine (DA) receptors, have been widely used to suppress hyper-aggression. However, the mechanisms underlying the effect of the antipsychotics remain incompletely understood. Objectives: We reviewed key steps in brain DA synthesis and summarized genetic and pharmacological evidence supporting the role of the mesolimbic DA system in aggression. Next, we discussed recent circuit studies that elucidate the DA action in modulating aggression-related brain regions. These lines of evidence collectively suggest that DA acts on different brain regions to facilitate aggression and self-learning, and signals the valence of the fighting experience.