Dichotomous Regulation of Social Behaviors by Nucleus Accumbens Neurons in Female and Male Syrian Hamsters

Social relationships, including dominance status, are powerful regulators of mental health, and social experiences impact the continued expression of these behaviors. However, very little is known about the neuronal mechanisms that regulate the positive reinforcing effects of aggression that underlie social dominance, including potential sex differences. To address this gap, we used viral-mediated gene expression in Syrian hamsters to investigate how nucleus accumbens neurons regulate behavioral adaptations caused by aggression and other social interactions in both males and females. We found that females, but not males, display an increase in the efficiency to establish aggression with repeated experience. Females also displayed a more rapid potentiation of calcium signals from nucleus accumbens neurons over repeated social interactions. Chemogenetic inhibition of nucleus accumbens neurons specifically decreased aggression in females. Optogenetic stimulation of excitatory synaptic input from prefrontal cortex to nucleus accumbens decreased social investigation in females, but increased social investigation and reduced aggression in males. Collectively, these studies suggest that the activity of nucleus accumbens neurons drives behavioral adaptations related to social interactions in general, and aggressive experience in particular, in opposite directions in females and males. This mechanism may contribute to the enhanced reward for social interactions in females compared to males, and help explain the sex differences in the susceptibility to disorders associated with deficits in social behavior.<b>Significance statement</b> Sex differences in neurobiology for social behaviors likely contribute to sex differences in the predisposition for many disorders. For the first time here, we report that neurons in the nucleus accumbens have opposite effects in the regulation of aggression and social affiliative behaviors for male and female Syrian hamsters. Moreover, with aggressive experience, females display a more pronounced potentiation of calcium signals from neurons in the nucleus accumbens compared to males, which may underlie the more pronounced sensitivity to the rewarding and reinforcing effects of aggression in females compared to males. These studies advance the understanding of sex differences in the reinforcing effects of social behaviors.