Dopamine and stress signalling interplay patterns social organization in mice

Abstract

The rules leading to the emergence of a social organization and the role of social ranking on normal and pathological behaviors remain elusive. Here we show that groups of four genetically identical male mice rapidly form enduring social ranking determined by precedence test and the sharing of beneficial resources. Highest ranked individuals are more anxious, more social and display increased spatial working memory. Whereas differences in anxiety between individuals appear after rank attainment, the higher sociability of top-ranked mice preexist. These behavioral differences correlate with physiological change. The highest ranked mice display indeed lower bursting activity of VTA dopamine neurons. The same animals are less responsive to preclinical models of stress behavioral disorders involving changes of dopamine system. They display lower locomotor sensitization to cocaine and are more resilient to repeated social defeat. The ablation of stress-elicited glucocorticoid receptor gene in dopaminoceptive neurons that affects the same pathological models, upwards the ranking status of mutant individuals. Altogether, these results support a role for social ranking in patterning interindividual VTA dopaminergic activity, behavioral responses and susceptibility to stressrelated psychopathologies.

Is It Possible to Shift from Down to Top Rank? A Focus on the Mesolimbic Dopaminergic System and Cocaine Abuse

“…The one that retreats backwards from the tube first is designated as the ‘loser’ or the subordinate [ 20 ]. In a study by [ 21 ], the submissive mice from four genetically identical male mice, determined by a tube test and the sharing of beneficial resources, had a significantly higher locomotor sensitization in response to repeated injections of cocaine in comparison to the dominant mice. This difference was maintained on the challenge day, thereby suggesting that dominant mice have a weaker behavioral response to cocaine.…”

“…Indeed, the administration of the D 2 receptors antagonist, sulpiride, has been shown to attenuate social dominance when the drug is given to high social class macaques and mice [ 68 ]. In addition, the highest ranked individuals exhibited a lower bursting activity of VTA DA neurons [ 21 ]. Importantly, differences in VTA dopaminergic neurons firing properties were observed as a reflection of individual behavioral differences when animals were gathered in large environments [ 69 ].…”

“…Individual differences in social behavior emerged after mice with low genetic diversity were living continuously in large groups [ 69 ]. A number of studies have shown that dominant-ranked mice exhibited a higher sociability than their subordinates [ 5 , 21 , 79 ]. Importantly, differences in sociability between the highest and lowest ranked mice were reported to pre-exist as a trait before gathering the animals into tetrads [ 21 ].…”

“…A number of studies have shown that dominant-ranked mice exhibited a higher sociability than their subordinates [ 5 , 21 , 79 ]. Importantly, differences in sociability between the highest and lowest ranked mice were reported to pre-exist as a trait before gathering the animals into tetrads [ 21 ]. These findings suggest that social dominance, or a high rank, may positively influence social motivation.…”

“…When a hierarchical social group was exposed to chronic social defeat stress, different results were found. Indeed, one study reported decreased social interactions in both high- and low-ranked mice [ 5 ], whereas a second study found that low-ranked mice were more likely to develop social aversion [ 21 ]. Based on the hypothesis that high-ranked mice would be the ones challenged by stress-exposure, it was found that dominant mice exhibited strong social avoidance, whereas subordinate mice were not affected [ 78 ].…”