Strain differences in post-castration sexual and aggressive behavior in male mice

David, Caroline D.; Wyrosdic, Brianna N.; Park, Jin Ho

doi:10.1016/j.bbr.2022.113747

Cited by 10 publications

(7 citation statements)

References 61 publications

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“…1I). This result is consistent with previous studies demonstrating the primary role of testosterone in female preference and sexual behavior (Amstislavskaya & Popova, 2004; David, Wyrosdic, & Park, 2022; Henley, Nunez, & Clemens, 2011; Pierman et al, 2008). Thus, the Two-intruders paradigm clearly reflects hormonal regulation behind mating behavior and can be utilized to assess the role of steroid metabolism and the associated deficits in social communication.…”

Section: Discussionsupporting

confidence: 93%

Investigating social communication in mice: a Two-intruders test approach

Morozova,

Boldyreva,

Borisova

et al. 2023

Preprint

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Understanding the complex dynamics of social communication behaviors, such as exploration, communication, courtship, mating, and aggression in animal models is crucial to reveal key neural and hormonal mechanisms underlying these behaviors. The Two-intruders test is designed to investigate residents’ behavior toward a male and female intruders. During this test imitating natural conditions, several aspects of social interaction were investigated: exploration, courtship, mating, and aggressive behavior. As mating and aggression involve overlapping neural circuits, the behavioral setup testing both behaviors is best at reflecting their competitive nature. Our findings demonstrate that male mice exhibit strong preference to communicate with a female intruder, which correlates with baseline testosterone levels of test males. Relevant female preference in the Two-intruder test was also found in BALB/c males. Behavioral breakdown revealed the anogenital sniffing as a key behavioral feature that discriminates test male behavior toward intruders of different genders. At the same time, female preference was accompanied by neuronal activation in the ventromedial hypothalamus. We demonstrate that odor recognition underlies preference toward females in male residents, as experimental anosmia reduced communication with a female intruder. However, there was no correlation between female animal preference in the contact Two-intruder test and smell preference in the social odor preference test. We assume the Two-intruders test setup to be a useful tool to study the neurological basis of social communication in animal models. Combined with odor preference tests, this experimental paradigm can help to decipher neural circuits involved in social deficiency phenotypes in animal models of human diseases.Significance StatementThe Two-intruders test proves to be a highly reproducible and robust approach to assess social communication in mice. We demonstrate that the results obtained in this experimental setting replicate in different mouse groups and strains. This test is indispensable in studies assessing the competitive nature of male- and female-driven behaviors and the underlying neural mechanisms. Resident’s social interactions in the described here set up reflects odor processing and circulating testosterone – the key physiological drivers of animal communication with conspecifics. While easy to perform, this test provides a broad spectrum of behavioral patterns to study in the models of complex neurological diseases. Largely overseen in the literature as compared to the resident-intruder setup, the Two-intruders test can provide superior performance when used to understand the neural mechanisms of mating, aggression and social communication.

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Section: Discussionsupporting

confidence: 93%

Investigating social communication in mice: a Two-intruders test approach

Morozova,

Boldyreva,

Borisova

et al. 2023

Preprint

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“…On top of that, one notable difference was that the mice in our study were 17 – 18 months old on their last MSB test, which is older than the traditional breeding age (Moreira et al ., 2015). Comparatively, the mice in previous studies were around 4 – 6 months of age on their last MSB test (David, Wyrosdic, & Park, 2022; David, Wyrosdic, Wan, et al ., 2022). This is a potential confound as ageing is known to impair MSB (Wilson et al ., 2018; Jesús et al ., 2022).…”

Section: Discussionmentioning

confidence: 97%

“…However, after they were provided social exposure, 20.59% of the males demonstrated consistent SIMSB at least 62 weeks post-orchidectomy. Because this current study differed from the previous SIMSB paradigms in our lab, we refer to the males that demonstrated SIMSB in this study as ‘SI persistent maters’ and those that did not as ‘SI non-maters’ to differentiate these mice from prior studies (David, Wyrosdic, & Park, 2022; David, Wyrosdic, Wan, et al ., 2022). Once SIMSB was reinstated, we then set out to test our original experiment which was to investigate neuron and microglia-specific immunoexpression using flow cytometry in the POA.…”

Section: Introductionmentioning

confidence: 99%

Neuron- and microglia-specific immunoexpression in steroid-independent male sexual behaviour in castrated B6D2F1 male mice

Chiang

Lipkin

McCusker

et al. 2022

Preprint

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Sexual behaviour is the sine qua non for procreation for several species and is traditionally viewed to be regulated by sex steroid hormones. However, several species exhibit steroid-independent sexual behaviour, and its molecular understanding is only beginning to be uncovered. We do not yet have a cell-specific understanding of the roles non-neuronal cells play in this phenomenon. Forty B6D2F1 hybrid male mice underwent orchidectomy and some of them exhibited consistent ejaculatory reflexes at least 62 weeks post-orchidectomy over 11 sexual behaviour tests (>180 minutes each), defined as steroid-independent (SI) maters (21.80%), and those that do not, defined as SI non-maters (25%). Using flow cytometry, we compared the preoptic area immunoexpression in NeuN+ neurons and Iba1+ microglia between SI maters and SI non-maters (n = 6 per group). We found neuronal immunoexpression up-regulated for amyloid precursor protein and androgen receptor, as well as down-regulated for glucocorticoid receptor. In conjunction, microglial immunoexpression of amyloid precursor protein up-regulated. These data suggest there are cell-specific immunoexpression changes including a role of non-neuronal cells in steroid-independent male sexual behaviour.

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“…This difference could also result from a difference between strains. Indeed, strain differences have been reported for many behaviors, such as anxiety‐like behavior and depressive‐like behavior, 47,48 and the regulation of male sexual behavior and territorial aggression by gonadal hormones highly depends on strain and experience 49,50 . Although most studies are currently conducted in C57Bl6 mice, showing that E4 produces similar effects on the behavior of CD1 mice suggests that these observations could be generalized to outbred strains.…”

Section: Discussionmentioning

confidence: 99%

Role of membrane estrogen receptor alpha (ERα) in the rapid regulation of male sexual behavior

de Bournonville,

Lemoine,

Foidart

et al. 2023

J Neuroendocrinology

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The activation of male sexual behavior depends on brain estrogen synthesis. Estrogens act through nuclear and membrane receptors producing effects within hours/days or seconds/minutes, respectively. In mice, estrogen receptor alpha (ERα) is the main estrogen receptor (ER) controlling the activation of male sexual behavior. Although neuroestrogens rapidly modulate mouse sexual behavior, it is not known whether these effects involve membrane ERα (mERα).This study combines two complementary approaches to address this question. C451A‐ERα mice carry an ERα that cannot signal at the membrane, while estetrol (E4) is a natural estrogen acting as an agonist on nuclear ERα but as an antagonist on membrane ERα. In wild‐type males, E4 decreased the number of mounts and intromissions after 10 min. In C451A‐ERα males, E4 also altered sexual performance but after 30 min. E4 did not affect time spent near the female in both wild‐type and C451A‐ERα mice. However, regardless of genotype, the aromatase inhibitor 1,4,6‐Androstatriene‐3,17‐dione (ATD) decreased both sexual performance and the time spent near the female after 10 and 30 min, confirming the key role of aromatization in the rapid control of sexual behavior and motivation.In conclusion, the shift in timing at which the effect of E4 is observed in mice lacking mERα suggests a role for mERα in the regulation of rapid effects of neuroestrogens on sexual performance, thus providing the first demonstration that E4 acts as an antagonist of a mER in the brain. The persisting effect of ATD on behavior in C451A‐ERα mice also suggests the implication of another ER.This article is protected by copyright. All rights reserved.

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Strain differences in post-castration sexual and aggressive behavior in male mice

Cited by 10 publications

References 61 publications

Investigating social communication in mice: a Two-intruders test approach

Investigating social communication in mice: a Two-intruders test approach

Neuron- and microglia-specific immunoexpression in steroid-independent male sexual behaviour in castrated B6D2F1 male mice

Role of membrane estrogen receptor alpha (ERα) in the rapid regulation of male sexual behavior

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