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CORT levels (ng/ml) for the IMP DOMS, IMP SUBS, INN DOM, and INN SUBS groups. Animals were confined to an elevated platform in a bright room for five minutes (which prior work indicated induced a moderate stress response) either 124 days (Groups IMP DOM and IMP SUB) or 32 days after colonization. Regardless of phenotype, colonization within approximately one month of the CORT assay promoted an increased CORT response to mild stress, which had dissipated within four months. Asterisks (*) indicate significant comparisons.
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Imposed social subordination, such as that which accompanies physical defeat or alienation, has been associated with impaired cognitive function in both human and non-human animals. Here we examined whether domain-specific and/or domain-general learning abilities (c.f. general intelligence) are differentially influenced by the imposition of social...
Context in source publication
Context 1
... four groups of animals [F(3,26) = 1.45, p = .25], and a planned comparison post hoc test confirmed that imposed subordinates (IMP SUBS) had Table 3 An unrotated principal component factor analysis of social behaviors and general learning abilities revealed a primary and secondary factor explaining 26% and 18% of the total variance, respectively. (Fig. 6). A t-test for independent samples between all subjects in the IMP groups and subjects in the INN groups was sig- nificant [t(1,28) = 2.08, p < .05], i.e., the INN groups (those who were made subordinate after learning was assessed) had higher levels of plasma CORT than subjects in the IMP groups. A t-test for indepen- dent samples ...
Citations
... The amygdaloid complex is known to connect two sensory systems (i.e., auditory and olfactory) that are sensitive to stress, which can lead to impairments in learning and memory (Soudry et al. 2011;Kiyokawa et al. 2012). Distress calls induce neuronal activation in the amygdala, resulting in an increase in neuronal excitability that may recall the fear memory of C. sphinx associated with distress calls (Chattarji et al. 2015) or may suppress exploratory behaviour to the novel odor, possibly by inhibiting amygdala output (Colas-Zelin et al. 2012). Thus, the bats exposed to distress calls/PBs of distress calls showed fewer feeding attempts and bouts towards novel odors. ...
This study was designed to test whether Cynopterus sphinx distress calls influence olfactory learning and memory in conspecifics. Bats were exposed to distress calls/playbacks (PBs) of distress calls/modified calls and were then trained to novel odors. Bats exposed to distress calls/PBs made significantly fewer feeding attempts and bouts of PBs exposed to modified calls, which significantly induced the expression of c-Fos in the caudomedial neostriatum (NCM) and the amygdala compared to bats exposed to modified calls and trained controls. However, the expression of c-Fos in the hippocampus was not significantly different between the experimental groups. Further, protein phosphatase-1 (PP-1) expression was significantly lower, and the expression levels of E1A homologue of CREB-binding protein (CBP) (P300), brain-derived neurotrophic factor (BDNF) and its tyrosine kinase B1 (TrkB1) receptor were significantly higher in the hippocampus of control/bats exposed to modified calls compared to distress calls/PBs of distress call-exposed bats. Exposure to the call possibly alters the reciprocal interaction between the amygdala and the hippocampus, accordingly regulating the expression levels of PP1, P300 and BDNF and its receptor TrkB1 following training to the novel odor. Thus, the learning and memory consolidation processes were disrupted and showed fewer feeding attempts and bouts. This model may be helpful for understanding the contributions of stressful social communications to human disorders.
... A series of studies carried out on different vertebrate species showed that performance in a learning task was related to an animal's level of aggressiveness, expressed by its status as winner or loser of an agonistic encounter, or by its rank within a social hierarchy. In general, studies have found a positive relationship between aggression and cognitive abilities, that is, more aggressive or dominant animals perform better in different cognitive tasks (Boogert et al. 2006;Fitchett and Collins 2005;Francia et al. 2006;Langley et al. 2018a, b;Colas-Zelin et al. 2012;Spritzer et al. 2004). However, there are a few studies where a lower social rank is associated with an improvement in learning and memory tasks (Barnard and Luo 2002;Bunnell et al. 1979;Keynan et al. 2015;Matzel et al. 2017;Monlen et al. 2015). ...
Cognitive abilities of an animal can be influenced by distinct social experiences. However, the extent of this modulation has not been addressed in different learning scenarios: are all tasks similarly affected by social experiences? In the present study, we analyzed the effect of social dominance in aversive and appetitive memory processes in the crab Neohelice granulata. In addition, we studied the influence of social isolation on memory ability. Social dominance experiments consisted of an agonistic phase immediately followed by a memory phase. During the agonistic phase, matched pairs of male crabs were staged in 10-min encounters and the dominant or subordinate condition of each member of the dyad was determined. During the memory phase, crabs were trained to acquire aversive or appetitive memory and tested 24 h later. Results showed that the agonistic encounter can modulate long-term memory according to the dominance condition in such a way that memory retention of subordinates results higher than their respective dominant. Remarkably, this result was found for both aversive and appetitive memory tasks. In addition, we found that isolated animals showed no memory retention when compared with animals that remained grouped. Altogether this work emphasizes the importance of social context as a modulator of cognitive abilities.
... To date, a number of studies have reported significant behavioral differences between dominant and subordinate mouse cage-mates (Hilakivi et al., 1989;Hilakivi-Clarke and Lister, 1992;Ferrari et al., 1998;Vekovishcheva and Sukhotina, 2000;Bartolomucci et al., 2001Bartolomucci et al., , 2004Palanza et al., 2001;Fitchett et al., 2005aFitchett et al., , 2009Sá-Rocha et al., 2006;Saldívar-González et al., 2007;Wang et al., 2011;Colas-Zelin et al., 2012;Horii et al., 2017;Larrieu et al., 2017;Zhou et al., 2017;Kunkel and Wang, 2018;Pallé et al., 2019;Varholick et al., 2019), but whether such differences generalize to male laboratory mice used in biomedical research remains unknown. To provide an initial evaluation of the relationship between social dominance status and behavioral phenotype, we conducted a systematic review and ran metaanalyses when sufficient data were available. ...
... By electronic search we identified 20 studies (i.e., published manuscripts) (Hilakivi et al., 1989;Hilakivi-Clarke and Lister, 1992;Ferrari et al., 1998;Vekovishcheva and Sukhotina, 2000;Bartolomucci et al., 2001Bartolomucci et al., , 2004Palanza et al., 2001;Fitchett et al., 2005aFitchett et al., , 2009Sá-Rocha et al., 2006;Saldívar-González et al., 2007;Wang et al., 2011;Colas-Zelin et al., 2012;Horii et al., 2017;Larrieu et al., 2017;Zhou et al., 2017;Kunkel and Wang, 2018;Varholick et al., 2018Varholick et al., , 2019Pallé et al., 2019) divided into 55 separate experiments that met our pre-specified inclusion criteria (Methods and Supplementary Text 1). These studies varied concerning strain, supplier, group-size, and whether littermates were housed together ( Table 1). ...
... Mice that engaged in more offensive behavior (e.g., attack, chase, mount, bite) compared to defensive behavior (e.g., flee, freeze, supine posture) were rated dominant, while those that showed more defensive behavior than offensive behavior were ranked subordinate. A total of four studies of these 12 also considered bite-wounds as a sign of dominance where the subordinate incurred bite-wounds and the dominant had none (Ferrari et al., 1998;Bartolomucci et al., 2001Bartolomucci et al., , 2004Colas-Zelin et al., 2012). This method of identifying dominance was used in two other studies without the provision of home-cage behavior (Hilakivi et al., 1989;Hilakivi-Clarke and Lister, 1992). ...
Background: Social dominance status (e.g., dominant or subordinate) is often associated with individual differences in behavior and physiology but is largely neglected in experimental designs and statistical analysis plans in biomedical animal research. In fact, the extent to which social dominance status affects common experimental outcomes is virtually unknown. Given the pervasive use of laboratory mice and culminating evidence of issues with reproducibility, understanding the role of social dominance status on common behavioral measures used in research may be of paramount importance.
Methods: To determine whether social dominance status—one facet of the social environment—contributes in a systematic way to standard measures of behavior in biomedical science, we conducted a systematic review of the existing literature searching the databases of PubMed, Embase, and Web of Science. Experiments were divided into several domains of behavior: exploration, anxiety, learned helplessness, cognition, social, and sensory behavior. Meta-analyses between experiments were conducted for the open field, elevated plus-maze, and Porsolt forced swim test.
Results: Of the 696 publications identified, a total of 55 experiments from 20 published studies met our pre-specified criteria. Study characteristics and reported results were highly heterogeneous across studies. A systematic review and meta-analyses, where possible, with these studies revealed little evidence for systematic phenotypic differences between dominant and subordinate male mice.
Conclusion: This finding contradicts the notion that social dominance status impacts behavior in significant ways, although the lack of an observed relationship may be attributable to study heterogeneity concerning strain, group-size, age, housing and husbandry conditions, and dominance assessment method. Therefore, further research considering these secondary sources of variation may be necessary to determine if social dominance generally impacts treatment effects in substantive ways.
... As such, the social environment of an animal likely plays an integral role in its survival strategy. Based on the results reported in the present study it is possible, for example, that an animal with a predisposition for high cognitive ability reared in an environment free of socially dominant peers may enjoy a high degree of survival-readiness (perhaps even enhanced by socialization, given the relationship between socialization and improved cognitive ability; see Voiker et al., 2005;Chida et al., 2006), while that same animal reared with exposure to social submission may experience decreased survival-readiness (given that social submission can impair cognitive performance; see Fitchett et al., 2005;Colas-Zelin et al., 2012). ...
Although genetically heterogeneous laboratory mice express individual differences in general cognitive ability (c.f., “intelligence”), it is unknown whether these differences are translated into behaviors that would promote survival. Here, genetically heterogeneous laboratory CD-1 mice were administered a series of cognitive tests from which their aggregate general cognitive ability was estimated. Subsequently, all animals were tested on nine (unlearned) tasks designed to assess behaviors that could contribute to survival in the wild. These tests included nest building (in the home and a novel environment), exploration, several indices of food finding, retrieval, and preference, and predator avoidance. Like general cognitive ability, a principal component analysis of these measures of survival-related behaviors (survival-readiness) yielded a general factor that accounted for ∼25% of the variance of mice across all of the tasks. An aggregate metric of general cognitive ability predicted an aggregate metric of general survival-readiness (r = 0.64), suggesting that more intelligent animals would be more suited for survival in natural environments. The nature of the pattern of correlations between general cognitive ability and performance on individual tests of survival-readiness (where tests conducted in previously unexplored contexts were more closely related to general cognitive ability) suggests the possibility that heightened attention (which is taxed in a novel environment) may be the common mediator of both of these classes of abilities, although other potential mediators are discussed. In total, these results suggest that performance on tasks that are explicitly intended to assess the likelihood of survival can be impacted by cognitive abilities.
... Social hierarchy establishment is highly conserved across social species, and in many cases low rankings in social hierarchy result in poor health outcomes through increased stress susceptibility as well as poor resource access (e.g., food, water, shelter, and mates), making social status a driving factor of natural selection [15]. While social dominance and submission in hierarchies may appear domain-specific from other cognitive modalities, the establishment of social hierarchies is highly dependent on a variety of cognitive functions, and some studies have indicated that environmental factors that shift rats to a subordinate phenotype also produce a host of other cognitive deficits [38]. This suggests that while dominant-submissive behaviors in the tube dominance test and cognitive behaviors in NOR, RAWM, and the Hebb-Williams maze may appear domain-specific, there exists a critical underlying link between them. ...
Binge drinking is common in adolescence. Rodent studies modeling adolescent binge drinking find persistent effects on the brain’s physiology, including increased expression of neuroimmune genes, impaired neurogenesis, and changes in behavioral flexibility. This study used females and males to investigate the effects of adolescent intermittent ethanol (AIE) on a battery of behaviors assessing spatial navigation using a radial arm water maze, working memory using the Hebb-Williams maze, non-spatial long-term memory using novel object recognition, and dominance using a tube dominance test. Results indicate that AIE impairs adult acquisition in spatial navigational learning with deficits predominantly driven by females. Surprisingly, AIE slowed the transition from random to serial search strategies in both sexes, suggesting AIE impairs flexibility in problem-solving processing. In the Hebb-Williams maze working memory task, adult AIE rats exhibited deficits in problem solving, resulting in more errors across the 12 maze configurations, independent of sex. Conversely, AIE decreased dominance behaviors in female rats, and at 7 months post-alcohol, female AIE rats continued to exhibit deficits in novel object recognition. These results suggest that cognitive-behavioral alterations after adolescent binge drinking persist well into middle age, despite abstinence. Future studies should focus on intervening treatment strategies in both females and males.
... Even in the absence of physical trauma, a range of studies has demonstrated that social defeat and subordination leads to changes in immune function, metabolism, and behavior [233]. Subordinate rats showed anxiety-like behaviors in the openfield, social interaction, novel object recognition, and judgment bias tests [234] and learning impairment in the passive avoidance task [235] and water-maze test [236,237]. However, the converse has been seen in mice with subordinates showing less anxiety [238], although learning was impaired [239]. ...
The use of animal models remains critical in preclinical and translational research. The reliability of the animal models and aspects of their validity is likely key to effective translation of findings to medicine. However, despite considerable uniformity in animal models brought about by control of genetics, there remain a number of social as well as innate and acquired behavioral characteristics of laboratory animals that may impact on research outcomes. These include the effects of strain and genetics, age and development, sex, personality and affective states, and social factors largely brought about by housing and husbandry. In addition, aspects of the testing environment may also influence research findings. A number of considerations resulting from the animals' innate and acquired behavioral characteristics as well as their social structures are described. Suggestions for minimizing the impact of these factors on research are provided.
... Les travaux évaluant les hiérarchies de dominance chez la souris ont mis en évidence des différences comportementales entre les animaux de différents statuts sociaux. Par exemple, les souris dominantes explorent généralement davantage un nouvel environnement que leurs conspécifiques subordonnées, bien que ces dernières présentent tendanciellement moins de comportements de type anxieux (D'Amato, 1988 ;Colas-Zelin et al., 2012 ;Horii et al., 2017 ;. Les animaux les plus agressifs présentent également une activité accrue dans un test de nage forcée, mais cette différence n'apparait qu'après que le rang social n'a été acquis . ...
L'organisation hiérarchique est la marque de nombreux vertébrés. Des associations entre rang social et état de santé sont signalées chez de nombreuses espèces incluant l’humain. Cependant, les mécanismes impliqués sont mal compris. La réponse au stress, spécifique au rang social chez de nombreux animaux, intervient dans de nombreuses pathologies psychiatriques. Ceci suggère un rôle de la réponse au stress dans le processus liant statut social et comportement. Mon travail de thèse vise à mieux comprendre les associations qui existent entre le rang social et le comportement individuel chez la souris. Mon travail vise à clarifier la direction de cette association en observant les conséquences du rang social sur le comportement et la vulnérabilité aux maladies psychiatriques, et réciproquement, en identifiant des marqueurs individuels précoces pouvant contribuer à façonner le destin social. Au niveau physiologique, je me concentre sur la réponse au stress et ses conséquences sur le système dopaminergique (DA), en tant que médiateur potentiel des phénotypes sociaux. Pour répondre à ces questions, j'ai évalué le rang social de mâles adultes C57BL/6 via des tests compétitifs. J'ai ensuite testé ces animaux pour l'anxiété, la sociabilité et les compétences cognitives, avant et après établissement hiérarchique. Nous avons enregistré l'activité électrophysiologique de cellules DA dans la région tégmentale ventrale. J'ai quantifié la libération de DA dans la voie mésocorticolimbique et testé les souris pour la dépression et la dépendance. Enfin, j’ai évalué les conséquences d’une inactivation du récepteur des glucocorticoïdes dans les cellules DAceptives pour la dominance sociale.
... In rodents, this experience has been shown to induce stress , compromise mental health (Prabhu et al. 2018), and impair learning (Goeckner et al. 1973;Spritzer et al. 2004). More recent studies in pairs of mice have confirmed that, indeed, learning ability deteriorates in submissive animals, which is not, however, directly due to stress (Fitchett et al. 2005;Colas-Zelin et al. 2012;Matzel et al. 2017). ...
... As for the first point, an involvement of stress in the regulation of socially modulated plasticity is probable and highly interesting . Studies in pairs of mice have shown that the ability to learn (Fitchett et al. 2005;Colas-Zelin et al. 2012;Matzel et al. 2017) as well as synaptic plasticity (Wang et al. 2016) actually degrade in submissive animals, which have an elevated basal corticosterone level McKittrick et al. 1995McKittrick et al. , 2000. Thus, stress is possibly involved as a mediating, but not alternative factor in blocking ODP in submissive mice. ...
We here show that social rank, as assessed by competition for a running wheel, influences ocular dominance plasticity in adult male mice. Dominant animals showed a clear ocular dominance shift after four days of MD, whereas their submissive cage mates did not. NMDA receptor activation, reduced GABA inhibition, and serotonin transmission were necessary for this plasticity, but not sufficient to explain the difference between dominant and submissive animals. In contrast, prefrontal dopamine concentration was higher in dominant than submissive mice, and systemic manipulation of dopamine transmission bidirectionally changed ocular dominance plasticity. Thus, we could show that a social hierarchical relationship influences ocular dominance plasticity in the visual cortex via higher-order cortices, most likely the medial prefrontal cortex. Further studies will be needed to elucidate the precise mechanisms by which this regulation takes place.
... rank and hierarchal organization) is associated with individual variability in behavior and physiology. For example, dominant mice tend to be more explorative than their subordinate cage-mates [17][18][19][20][21][22][23] . Also, a recent experiment demonstrated that alpha ranked mice are more susceptible to develop depression-like behavior following repeated social defeat 24 . ...
... Also, a recent experiment demonstrated that alpha ranked mice are more susceptible to develop depression-like behavior following repeated social defeat 24 . However, no clear differences have been reported with respect to other phenotypic traits, including; anxiety 18,[24][25][26][27][28] , learning 18,29 , social behavior 30 , sensory behavior 18,26,28 , and immune function 17,31,32 . One possible explanation for the absence of a clear difference in phenotype beyond exploratory behavior is that many studies overlook dominance rank in conjunction with different types of dominance hierarchies and assume that all cages form transitive hierarchies with a clear rank order. ...
... Also, a recent experiment demonstrated that alpha ranked mice are more susceptible to develop depression-like behavior following repeated social defeat 24 . However, no clear differences have been reported with respect to other phenotypic traits, including; anxiety 18,[24][25][26][27][28] , learning 18,29 , social behavior 30 , sensory behavior 18,26,28 , and immune function 17,31,32 . One possible explanation for the absence of a clear difference in phenotype beyond exploratory behavior is that many studies overlook dominance rank in conjunction with different types of dominance hierarchies and assume that all cages form transitive hierarchies with a clear rank order. ...
A tacit assumption in laboratory animal research is that animals housed within the same cage or pen are phenotypically more similar than animals from different cages or pens, due to their shared housing environment. This assumption drives experimental design, randomization schemes, and statistical analysis plans, while neglecting social context. Here, we examined whether a domain of social context—social dominance—accounted for more phenotypic variation in mice than cage-identity. First, we determined that cages of mice could be categorized into one of three dominance hierarchies with varying degrees of dominance behavior between cage-mates, and low levels of agonistic behavior in the home-cage. Most groups formed dynamic hierarchies with unclear ranks, contrasting with recent accounts of stable transitive hierarchies in groups of mice. Next, we measured some phenotypic traits, and found that social dominance (i.e. dominance hierarchy type and degree of dominance behavior) consistently accounted for some phenotypic variation in all outcome measures, while cage-identity accounted for phenotypic variation in some measures but virtually no variation in others. These findings highlight the importance of considering biologically relevant factors, such as social dominance, in experimental designs and statistical plans.
... In the case of social defeat during adolescence, studies have reported an increase (Kinsey et al. 2007;Huang et al. 2013;Iñiguez et al. 2014) or no changes in the anxiety profile (Watt et al. 2009). As with the results obtained in anxiety, social defeat during adulthood induced a performance detriment in the Hebb-Williams maze (García-Pardo et al. 2015), in agreement with previous results (Colas-Zelin et al. 2012;Jin et al. 2015;Novick et al. 2013;Patki et al. 2013Patki et al. , 2014. Although all animals learned how to reach the goal, socially defeated adult mice needed more time to exit the maze, suggesting that the acquisition of learning had been slowed down by exposure to RSD. ...
Rationale
Previous studies have demonstrated that repeated social defeat (RSD) stress only induces cognitive deficits when experienced during adulthood. However, RSD increases cocaine-rewarding effects in adult and adolescent mice, inducing different expressions of proBDNF in the ventral tegmental area.
Objective
The aim of the present study was to evaluate the effect of cocaine administration in socially defeated adult or adolescent mice on learning, memory, and anxiety. Additionally, the role of BDNF was also studied.
Methods
Adolescent and young adult mice were exposed to four episodes of social defeat or exploration (control), being treated with a daily injection of four doses of saline or 1 mg/kg of cocaine 3 weeks after the last social defeat. Other groups were treated with the TrkB receptor antagonist ANA-12 during this 21-day period. After this treatment, their cognitive and anxiogenic profiles were evaluated, along with the expression of BDNF, pCREB, and pERK1/2 in the dentate gyrus (DG) and basolateral amygdala (BLA).
Results
Cocaine induced an increased expression of pCREB and BDNF in the DG and BLA only in defeated animals. Although RSD did not affect memory, the administration of cocaine induced memory impairments only in defeated animals. Defeated adult mice needed more time to complete the mazes, and this effect was counteracted by cocaine administration. RSD induced anxiogenic effects only when experienced during adulthood and cocaine induced a general anxiolytic effect. Blockade of Trkb decreased memory retention without affecting spatial learning and modified anxiety on non-stressed mice depending on their age.
Conclusion
Our results demonstrate that the long-lasting effects of social defeat on anxiety and cognition are modulated by cocaine administration. Our results highlight that the BDNF signaling pathway could be a target to counteract the effects of cocaine on socially stressed subjects.
