Search

Simple Summary: Animals often inflict bite wounds in laboratory housing, compromising animal welfare and, potentially, experimental results. For example, 1.5–14% of male laboratory mice (Mus musculus) obtain bite wounds over the course of a year. Recently, spiny mice (Acomys cahirinus) have become more popular in laboratory research for their regenerative healing and menstrual cycling, but we noticed frequent severe wounding in males and females in our colony—likely related to their relatively weak skin. Thus, we recorded the frequency and severity of bite wounding in our colony for one year and found that 46% of spiny mice had at least one bite wound, regardless of sex. The bite wounds in females were less severe, with single wounds on the rump, while males more often had multiple wounds on their anterior and rump. In a separate study, both sexes established stable dominance structures, with most of the fights occurring at the start of the active/dark cycle. Aged animals greater than 22 months old were never observed fighting, and the study on bite wounding suggested they also do not inflict bite wounds. These results have implications for both spiny mouse welfare and experimental results using spiny mice since repeated physical trauma can affect healing and menstrual cycling in mice and humans. Bite wounds due to aggression in male laboratory mice (Mus musculus) are a major welfare concern, often leading to attrition, chronic activation of the innate immune system, and significant impacts on the experimental results derived from the use of these animals as models. Bite wounding within the home-cage of spiny mice (Acomys cahirinus)—a valuable research model for wound healing and menstruation—is poorly characterized. While we have anecdotally observed frequent bite wounding in Acomys, the frequency of aggression within the home-cage, the severity of the bite wounds, and the types of dominance structures remain unstudied. Here, we report that 46% of Acomys cages in our colony had at least one bite wound over the course of a year and that same-sex pairs fought in the home-cage 10% of the time during their dark/active phase. Both sexes inflicted wounds and frequently engaged in agonistic behaviors, even with stable dominance structures. We found that females inflicted less severe bite wounds in same-sex housing. Also, aged females in same-sex pairs were never observed fighting, and no bite wounds were observed in aged Acomys. These results suggest that we should consider whether bite wounding negatively impacts our experimental results since physical trauma is known to alter menstrual cycling and healing. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) abuse is associated with a spectrum of behavioral consequences, among which heightened aggression presents a significant challenge. However, the causal role of METH's impact in aggression and its target circuit mechanisms remains largely unknown. We established an acute METH exposure-aggression mouse model to investigate the role of ventral tegmental area (VTA) dopaminergic neurons and ventral medial hypothalamus VMH glutamatergic neuron. Our findings revealed that METH-induced VTA dopamine excitability activates the ventromedial hypothalamus (VMH) glutamatergic neurons, contributing to pathological aggression. Notably, we uncovered a dopaminergic transmission within the VTA-VMH circuit that exclusively functioned under METH influence. This dopaminergic pathway emerged as a potential key player in enabling dopamine-related pathological aggression, with heightened dopaminergic excitability implicated in various psychiatric symptoms. Also, the modulatory function of this pathway opens new possibilities for targeted therapeutic strategies for intervention to improve treatment in METH abuse and may have broader implications for addressing pathological aggression syndromes. • Elevated VTA dopaminergic excitability emerges as a key contributor to METH-induced aggression. • Dopamine presence in the VMH is exclusive to METH influence. • The VTA-VMH circuit is engaged, playing a dual role in both the development and modulation of METH-induced aggression. [ABSTRACT FROM AUTHOR]

The enzyme steroid 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into the potent androgen 5α-dihydrotestosterone. Previous investigations showed that 5αR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5αR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5αR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses. Furthermore, male 5αR2 KO mice exhibited reduced D 2 -like dopamine receptor binding in the shell of the nucleus accumbens – a well-recognized molecular signature of social dominance. Collectively, these results suggest that 5αR2 is involved in the establishment of social dominance and its behavioral manifestations. Further studies are warranted to understand how the metabolic actions of 5αR2 on steroid profile may be implicated in social ranking, impulse control, and the modulation of dopamine receptor expression in the nucleus accumbens. [ABSTRACT FROM AUTHOR]

Depression is one of the most common chronic mental disorders, which is a leading cause of morbidity and mortality in patients. Depression often leads to offensive and defensive behaviours but the underlying mechanisms are not known. We propose that the aggressive behaviours in depression can be modelled in animal experiments. In this study, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm and detected aggressive and social dominance behaviours in rodents by resident/intruder test and social dominance tube test (SDTT), respectively. The CUMS-exposed mice showed increased defensive, offensive and aggressive behaviours in the resident-intruder test. In the SDTT, these mice showed enhanced social dominance. These alterations were associated with reduced MAP-2 expression in the hippocampus while no difference in β-tubulin expression was detected. In addition, the treatment of anti-depressant fluoxetine reversed the aggressive behaviours without reducing the social dominance behaviour induced by CUMS. However, fluoxetine did effectively reverted the changes in MAP-2 expression in the hippocampus. In addition, the nonspecific tricyclic antipsychotic drug, clozapine, reversed all symptoms of CUMS-exposed mice including aggressive tendencies, impulsive violence, social dominance behaviour and MAP-2 expression in the hippocampus. The results suggests that social maladjustment such as competition and social dominance are likely related to the dopaminergic system rather than the serotonergic system and the hippocampal dendritic structure protein MAP-2. Thus, dominance can be separated from aggression. This study shows that aggression/hostility and social hierarchy/dominance are increased in the CUMS-exposed mice and thus provide an excellent model for further study in the diagnosis and the treatment of depression-associated aggression. [ABSTRACT FROM AUTHOR]

Summary: Gonadal hormones mediate both affiliative and agonistic social interactions. Research in estrogen receptor alpha (ERα) or beta (ERβ) knockout (KO) mice suggests that ERα increases and ERβ decreases male aggression, while the opposite is found for female ERαKO and ERβKO mice. Using a detailed behavioural analysis of the resident-intruder test, we have shown that the ERβ selective agonist WAY-200070 increased agonistic behaviours, such as aggressive grooming and pushing down a gonadectomized (gonadex) intruder, in gonadally intact but not gonadex male and female resident mice, while leaving attacks unaffected. The role of acute activation of ERα in agonistic behaviour in adult non-KO CD1 mice is presently unknown. The current study assesses the effects of the ERα selective agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) on the social and agonistic responses of gonadally intact and gonadex male and female CD1 mice to a gonadex, same-sex intruder. PPT had few effects in gonadally intact mice, but seems to increase sex-typical aggression (i.e., attacks in males, other dominance-related behaviours in females) in gonadex mice. In untreated mice, we confirmed our previous findings that gonadally intact males attacked the intruder more than females, but females spent more time engaged in agonistic behaviour than males. As in our previous results, we observed that gonadex mice generally show behaviour patterns more like those of the gonadally intact opposite sex, while leaving overall levels of agonistic behaviour unaffected. Taken together, our current and previous results show that exogenous activation of ERα had no effects in gonadally intact mice, but increased sex-typical agonistic behaviour in gonadex mice, while ERβ had no effects in gonadex mice, but increased non-attack agonistic behaviour in gonadally intact animals. This suggests that, as in social recognition, ERα may be necessary for the activation of agonistic responses, while ERβ may play a modulatory role. [Copyright &y& Elsevier]

Summary: Affiliative and agonistic social interactions are mediated by gonadal hormones. Research with estrogen receptor alpha (ERα) or beta (ERβ) knockout (KO) mice show that long-term inactivation of ERα decreases, while inactivation of ERβ increases, male aggression. Opposite effects were found in female αERKO and βERKO mice. The role of acute activation of ERα or ERβ in the agonistic responses of adult non-KO mice is unknown. We report here the effects of the ERβ selective agonist WAY-200070 on agonistic and social behavior in gonadally intact and gonadectomized (gonadex) male and female CD-1 mice towards a gonadex, same-sex intruder. All 15min resident–intruder tests were videotaped for comprehensive behavioral analysis. Separate analyses assessed: (1) effects of WAY-200070 on each sex and gonadal condition; (2) differences between sexes, and between gonadally intact and gonadex mice, in untreated animals. Results show that in gonadally intact male and female mice, WAY-200070 increased agonistic behaviors such as pushing down the intruder and aggressive grooming, while leaving attacks unaffected. In untreated mice, males attacked more than females, and gonadex animals showed less agonistic behavior than same-sex, gonadally intact mice. Overall, our detailed behavioral analysis suggested that in gonadally intact male and female mice, ERβ mediates patterns of agonistic behavior that are not directly involved in attacks. This suggests that specific aspects of aggressive behavior are acutely mediated by ERβ in adult mice. Our results also showed that, in resident–intruder tests, female mice spend as much time in intrasexual agonistic interactions as males, but use agonistic behaviors that involve extremely low levels of direct attacks. This non-attack aggression in females is increased by acute activation of ERβ. Thus, acute activation of ERβ similarly mediates agonistic behavior in adult male and female CD-1 mice. [Copyright &y& Elsevier]

Abstract: We have previously reported that mice with a targeted disruption of their vasopressin 1b receptor gene, Avpr1b, have mild impairments in social recognition and reduced aggression. The reductions in aggression are limited to social forms of aggression, i.e., maternal and inter-male aggression, while predatory aggression remains unaffected. To further clarify the role of the Avpr1b in the regulation of social behavior we first examined anxiety-like and depression-like behaviors in Avpr1b knockout (Avpr1b −/−) mice. We then went on to test the ability of Avpr1b −/− mice to form dominance hierarchies. No major differences were found between Avpr1b −/− and wildtype mice in anxiety-like behaviors, as measured using an elevated plus maze and an open field test, or depression-like behaviors, as measured using a forced swim test. In the social dominance study we found that Avpr1b −/− mice are able to form dominance hierarchies, though in early hierarchy formation dominant Avpr1b −/− mice display significantly more mounting behavior on Day 1 of testing compared to wildtype controls. Further, non-socially dominant Avpr1b −/− mice spend less time engaged in attack behavior than wildtype controls. These findings suggest that while Avpr1b −/− mice may be able to form dominance hierarchies they appear to employ alternate strategies. [Copyright &y& Elsevier]

The diallel cross genetic design was employed to determine the pattern of inheritance of male--male agonistic behavior in laboratory mice. The results indicated strong strain differences in agonistic behaviors and strain ranks that replicated previous findings. The genetic analysis showed the presence of additive and nondirectional dominance effects on the behaviors measured. This pattern has been characterized as indicating the action of stabilizing selection and indicates that the trait has not been under directional selection. [ABSTRACT FROM AUTHOR]