Dopamine Neuron Activity and Stress Signaling as Links Between Social Hierarchy and Psychopathology Vulnerability

BackgroundSocial status in human, generally reflected by socioeconomic status, has been associated, when constrained, with heightened vulnerability to pathologies including psychiatric diseases. Social hierarchy in mice translates into individual and interdependent behavioural strategies of animals within a group. The rules leading to the emergence of a social organization are elusive and detangling the contribution of social status from other factors, whether environmental or genetic, to normal and pathological behaviours remains challenging.MethodsWe investigated the mechanisms shaping the emergence of a social hierarchy in isogenic C57Bl/6 mice raised by groups of four using conditional mutant mouse models and chemogenetic manipulation of dopamine midbrain neuronal activity. We further studied the evolution of behavioural traits and the vulnerability to psychopathological-like phenotypes according to the social status of the animals.ResultsHigher sociability predetermined higher social hierarchy in the colony. Upon hierarchy establishment, higher ranked mice showed increased anxiety and better cognitive abilities in a working memory task. Strikingly, the higher ranked mice displayed a reduced activity of dopaminergic neurons within the ventral tegmental area, paired with a decrease behavioural response to cocaine and a decreased vulnerability to depressive-like behaviours following repeated social defeats. The pharmacogenetic inhibition of this neuronal population and the genetic inactivation of glucocorticoid receptor signalling in dopamine-sensing brain areas that resulted in decreased dopaminergic activity promoted the accession to higher social ranks.ConclusionsDopamine activity and its modulation by the stress response shapes social organization in mice, potentially linking interindividual and social status differences in vulnerability to psychopathologies.