Nucleus accumbens dichotomically controls social dominance in male mice

AbstractSocial hierarchy in social species is usually established through competitive encounters with conspecifics. It determines the access to limited resources and, thus, leads to reduced fights among individuals within a group. Despite the known importance of social rank for health and well-being, the knowledge about the processes underlying rank attainment remains limited. Previous studies have highlighted the nucleus accumbens (NAc) as a key brain region in the attainment of social hierarchies in rodents. In addition, glucocorticoids and the glucocorticoid receptor (GR) have been implicated in the establishment of social hierarchies and social aversion. However, whether GR in the NAc is involved in social dominance is not yet known. To address this question, we first established that expression levels of GR in the NAc of high anxious, submissive-prone rats are lower than that of their low anxious, dominant-prone counterparts. Furthermore, virally-induced downregulation of GR expression in the NAc in rats led to an improvement of social dominance rank. We found a similar result in a cell-specific mouse model lacking GR in dopaminoceptive neurons (i.e., neurons containing dopamine receptors). Indeed, when cohabitating in dyads of mixed genotypes, mice deficient for GR in dopaminoceptive neurons had a higher probability to become dominant than wild-type mice. Overall, our results highlight GR in the NAc and in dopaminoceptive neurons as an important regulator of social rank attainment.

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Loss of muscarinic M5 receptor function manifests disparate impairments in exploratory behavior in male and female mice despite common dopamine regulation

10.1101/2021.07.11.451965 ◽

2021 ◽

Author(s):

John A Razidlo ◽

Skylar ML Fausner ◽

Liuchang C Wang ◽

Salahudeen A Mirza ◽

Veronica A Alvarez ◽

...

Keyword(s):

Nucleus Accumbens ◽

Therapeutic Target ◽

Acetylcholine Receptors ◽

Muscarinic Acetylcholine Receptors ◽

Dopamine Neurons ◽

Male Mice ◽

Male And Female ◽

Female Mice ◽

Attractive Therapeutic Target ◽

Dopamine Transmission

There are five cloned muscarinic acetylcholine receptors (M1-M5). Of these, the muscarinic type 5 receptor (M5) is the only one localized to dopamine neurons in the ventral tegmental area and substantia nigra. Unlike M1-M4, the M5 receptor has relatively restricted expression in the brain, making it an attractive therapeutic target. Here we performed an in-depth characterization of M5-dependent potentiation of dopamine transmission in the nucleus accumbens and accompanying exploratory behaviors in male and female mice. We show that M5 receptors potentiate dopamine transmission by acting directly on the terminals within the nucleus accumbens. Using the agonist oxotremorine, we revealed a unique concentration response curve and a sensitivity to repeated stressor exposure. We found that constitutive deletion of M5 receptors reduced exploration of the center of an open field while at the same time impairing normal habituation only in male mice. In addition, M5 deletion reduced exploration of salient stimuli, especially under conditions of high novelty, yet had no effect on hedonia. We conclude that M5 receptors are critical for both engaging with the environment and updating behavioral output in responses to the environment cues, specifically in male mice. A cardinal feature of mood and anxiety disorders is a withdrawal from the environment. These data indicate that boosting M5 receptor activity may be a useful therapeutic target for ameliorating these symptoms of depression and anxiety.

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Faculty Opinions recommendation of Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727822618.793554193 ◽

2018 ◽

Author(s):

E Ronald de Kloet

Keyword(s):

Nucleus Accumbens ◽

Mitochondrial Function ◽

Social Dominance ◽

D1 Receptors ◽

Dopamine D1 Receptors

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The role of medial prefrontal neurons in social dominance and competitive success in groups of male mice

IBRO Reports ◽

10.1016/j.ibror.2019.07.635 ◽

2019 ◽

Vol 6 ◽

pp. S203

Author(s):

Songjun Li ◽

Leah Strahs ◽

Lance Johnson ◽

Ziv Williams

Keyword(s):

Social Dominance ◽

Male Mice ◽

Competitive Success

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Stress decreases serotonin tone in the nucleus accumbens in male mice to promote aversion and potentiate cocaine preference via decreased stimulation of 5-HT1B receptors

Neuropsychopharmacology ◽

10.1038/s41386-021-01178-0 ◽

2021 ◽

Author(s):

Harrison M. Fontaine ◽

Phillip R. Silva ◽

Carlie Neiswanger ◽

Rachelle Tran ◽

Antony D. Abraham ◽

...

Keyword(s):

Nucleus Accumbens ◽

Male Mice ◽

Stimulation Of

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Group housing and social dominance hierarchy affect circadian activity patterns in mice

Royal Society Open Science ◽

10.1098/rsos.201985 ◽

2021 ◽

Vol 8 (2) ◽

pp. 201985

Author(s):

Yuri Robbers ◽

Mayke M. H. Tersteeg ◽

Johanna H. Meijer ◽

Claudia P. Coomans

Keyword(s):

Social Environment ◽

Social Dominance ◽

Dominance Hierarchy ◽

Activity Patterns ◽

Dominance Rank ◽

Dominant Male ◽

Group Housing ◽

Male Mice ◽

Female Mice ◽

The Social

In this study, we investigated the effect of social environment on circadian patterns in activity by group housing either six male or six female mice together in a cage, under regular light–dark cycles. Based on the interactions among the animals, the social dominance rank of individual mice was quantitatively established by calculating Elo ratings. Our results indicated that, during our experiment, the social dominance hierarchy was rapidly established, stable yet complex, often showing more than one dominant mouse and several subordinate mice. Moreover, we found that especially dominant male mice, but not female mice, displayed a significantly higher fraction of their activity during daytime. This resulted in reduced rhythm amplitude in dominant males. After division into separate cages, male mice showed an enhancement of their 24 h rhythm, due to lower daytime activity. Recordings of several physiological parameters showed no evidence for reduced health as a potential consequence of reduced rhythm amplitude. For female mice, transfer to individual housing did not affect their daily activity pattern. We conclude that 24 h rhythms under light–dark cycles are influenced by the social environment in males but not in females, and lead to a decrement in behavioural rhythm amplitude that is larger in dominant mice.

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The effects of castration and androgen on the social dominance of BALB/cJ male mice

Physiological Psychology ◽

10.3758/bf03333000 ◽

1974 ◽

Vol 2 (1) ◽

pp. 93-98 ◽

Cited By ~ 9

Author(s):

C. T. Lee ◽

J. N. Naranjo

Keyword(s):

Social Dominance ◽

Male Mice ◽

The Social

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An Adolescent Sensitive Period for Social Dominance Hierarchy Plasticity Is Regulated by Cortical Plasticity Modulators in Mice

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.676308 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lucy K. Bicks ◽

Michelle Peng ◽

Alana Taub ◽

Schahram Akbarian ◽

Hirofumi Morishita

Keyword(s):

Social Dominance ◽

Dominance Hierarchy ◽

Behavioral Plasticity ◽

Cortical Plasticity ◽

Developmental Trajectory ◽

Adolescent Male ◽

Sensitive Period ◽

Male Mice ◽

Dominance Hierarchies ◽

The Social

Social dominance hierarchies are a common adaptation to group living and exist across a broad range of the animal kingdom. Social dominance is known to rely on the prefrontal cortex (PFC), a brain region that shows a protracted developmental trajectory in mice. However, it is unknown to what extent the social dominance hierarchy is plastic across postnatal development and how it is regulated. Here we identified a sensitive period for experience-dependent social dominance plasticity in adolescent male mice, which is regulated by mechanisms that affect cortical plasticity. We show that social dominance hierarchies in male mice are already formed at weaning and are highly stable into adulthood. However, one experience of forced losing significantly reduces social dominance during the adolescent period but not in adulthood, suggesting adolescence as a sensitive period for experience-dependent social dominance plasticity. Notably, robust adolescent plasticity can be prolonged into adulthood by genetic deletion of Lynx1, a molecular brake that normally limits cortical plasticity through modulation of cortical nicotinic signaling. This plasticity is associated with increased activation of established nodes of the social dominance network including dorsal medial PFC and medial dorsal thalamus evidenced by increased c-Fos. Pharmacologically mediated elevation of cortical plasticity by valproic acid rapidly destabilizes the hierarchy of adult wildtype animals. These findings provide insight into mechanisms through which increased behavioral plasticity may be achieved to improve therapeutic recovery from psychiatric disorders that are associated with social deficits.

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