scholarly journals Social status influences normal and pathological behaviors in mice, a role for dopamine and stress signaling

2019 ◽  
Author(s):  
Dorian Battivelli ◽  
Cécile Vernochet ◽  
Claire Nguyen ◽  
Soumee Bhattacharya ◽  
Abdallah Zayed ◽  
...  

SummaryThe 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 stress-related psychopathologies.

2018 ◽  
Vol 115 (40) ◽  
pp. E9479-E9488 ◽  
Author(s):  
Robert A. Rifkin ◽  
Deborah Huyghe ◽  
Xiaofan Li ◽  
Manasa Parakala ◽  
Erin Aisenberg ◽  
...  

GABABR-dependent activation of G protein-gated inwardly rectifying potassium channels (GIRK or KIR3) provides a well-known source of inhibition in the brain, but the details on how this important inhibitory pathway affects neural circuits are lacking. We used sorting nexin 27 (SNX27), an endosomal adaptor protein that associates with GIRK2c and GIRK3 subunits, to probe the role of GIRK channels in reward circuits. A conditional knockout of SNX27 in both substantia nigra pars compacta and ventral tegmental area (VTA) dopamine neurons leads to markedly smaller GABABR- and dopamine D2R-activated GIRK currents, as well as to suprasensitivity to cocaine-induced locomotor sensitization. Expression of the SNX27-insensitive GIRK2a subunit in SNX27-deficient VTA dopamine neurons restored GIRK currents and GABABR-dependent inhibition of spike firing, while also resetting the mouse’s sensitivity to cocaine-dependent sensitization. These results establish a link between slow inhibition mediated by GIRK channels in VTA dopamine neurons and cocaine addiction, revealing a therapeutic target for treating addiction.


2016 ◽  
Vol 107 ◽  
pp. 8-13 ◽  
Author(s):  
Katja Kerstin Schneider ◽  
Christian Frings ◽  
Jobst Meyer ◽  
Andrea B. Schote

2017 ◽  
Vol 29 (5) ◽  
pp. 1517-1538 ◽  
Author(s):  
Sarah R. Moore ◽  
Lisa M. McEwen ◽  
Jill Quirt ◽  
Alex Morin ◽  
Sarah M. Mah ◽  
...  

AbstractAnimal models of early postnatal mother–infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4–5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), μ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.


2006 ◽  
Vol 17 (10) ◽  
pp. 386 ◽  
Author(s):  
Filip Van Den Eede ◽  
Dirk van West ◽  
Christine Van Broeckhoven ◽  
Stephan J. Claes

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