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      Indispensable role of the oxytocin receptor for allogrooming toward socially distressed cage mates in female mice

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          Abstract

          Social contact reduces stress responses in social animals. Mice have been shown to show allogrooming behaviour toward distressed conspecifics. However, the precise neuronal mechanisms underlying allogrooming behaviour remain unclear. In the present study, we examined whether mice show allogrooming behaviour towards distressed conspecifics in a social defeat model and we also determined whether oxytocin receptor‐expressing neurons were activated during allogrooming by examining the expression of c‐Fos protein, a marker of neurone activation. Mice showed allogrooming behaviour toward socially defeated conspecifics. After allogrooming behaviour, the percentages of oxytocin receptor‐expressing neurones expressing c‐Fos protein were significantly increased in the anterior olfactory nucleus, cingulate cortex, insular cortex, lateral septum and medial amygdala of female mice, suggesting that oxytocin receptor‐expressing neurones in these areas were activated during allogrooming behaviour toward distressed conspecifics. The duration of allogrooming was correlated with the percentages of oxytocin receptor‐expressing neurones expressing c‐Fos protein in the anterior olfactory nucleus, insular cortex, lateral septum and medial amygdala. In oxytocin receptor‐deficient mice, allogrooming behaviour toward socially defeated cage mates was markedly reduced in female mice but not in male mice, indicating the importance of the oxytocin receptor for allogrooming behaviour in female mice toward distressed conspecifics. The results suggest that the oxytocin receptor, possibly in the anterior olfactory nucleus, insular cortex, lateral septum and/or medial amygdala, facilitates allogrooming behaviour toward socially distressed familiar conspecifics in female mice.

          Abstract

          Mice showed allogrooming behaviour towards distressed conspecifics in a social defeat model. Allogrooming behaviour was correlated with activation of oxytocin receptor‐expressing neurones in the anterior olfactory nucleus, insular cortex, lateral septum and medial amygdala. Oxytocin receptor‐deficient females, but not males, showed impairment of allogrooming behaviour, indicating a sexual difference in neural mechanisms of allogrooming.

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          A standardized protocol for repeated social defeat stress in mice.

          A major impediment to novel drug development has been the paucity of animal models that accurately reflect symptoms of affective disorders. In animal models, prolonged social stress has proven to be useful in understanding the molecular mechanisms underlying affective-like disorders. When considering experimental approaches for studying depression, social defeat stress, in particular, has been shown to have excellent etiological, predictive, discriminative and face validity. Described here is a protocol whereby C57BL/6J mice that are repeatedly subjected to bouts of social defeat by a larger and aggressive CD-1 mouse results in the development of a clear depressive-like syndrome, characterized by enduring deficits in social interactions. Specifically, the protocol consists of three important stages, beginning with the selection of aggressive CD-1 mice, followed by agonistic social confrontations between the CD-1 and C57BL/6J mice, and concluding with the confirmation of social avoidance in subordinate C57BL/6J mice. The automated detection of social avoidance allows a marked increase in throughput, reproducibility and quantitative analysis. This protocol is highly adaptable, but in its most common form it requires 3-4 weeks for completion.
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            Sex differences in the brain: implications for explaining autism.

            Empathizing is the capacity to predict and to respond to the behavior of agents (usually people) by inferring their mental states and responding to these with an appropriate emotion. Systemizing is the capacity to predict and to respond to the behavior of nonagentive deterministic systems by analyzing input-operation-output relations and inferring the rules that govern such systems. At a population level, females are stronger empathizers and males are stronger systemizers. The "extreme male brain" theory posits that autism represents an extreme of the male pattern (impaired empathizing and enhanced systemizing). Here we suggest that specific aspects of autistic neuroanatomy may also be extremes of typical male neuroanatomy.
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              The neural basis of empathy.

              Empathy--the ability to share the feelings of others--is fundamental to our emotional and social lives. Previous human imaging studies focusing on empathy for others' pain have consistently shown activations in regions also involved in the direct pain experience, particularly anterior insula and anterior and midcingulate cortex. These findings suggest that empathy is, in part, based on shared representations for firsthand and vicarious experiences of affective states. Empathic responses are not static but can be modulated by person characteristics, such as degree of alexithymia. It has also been shown that contextual appraisal, including perceived fairness or group membership of others, may modulate empathic neuronal activations. Empathy often involves coactivations in further networks associated with social cognition, depending on the specific situation and information available in the environment. Empathy-related insular and cingulate activity may reflect domain-general computations representing and predicting feeling states in self and others, likely guiding adaptive homeostatic responses and goal-directed behavior in dynamic social contexts.
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                Author and article information

                Contributors
                y-masa@jichi.ac.jp , tonaka@jichi.ac.jp
                tonaka@jichi.ac.jp
                Journal
                J Neuroendocrinol
                J Neuroendocrinol
                10.1111/(ISSN)1365-2826
                JNE
                Journal of Neuroendocrinology
                John Wiley and Sons Inc. (Hoboken )
                0953-8194
                1365-2826
                31 May 2021
                June 2021
                : 33
                : 6 ( doiID: 10.1111/jne.v33.6 )
                : e12980
                Affiliations
                [ 1 ] Division of Brain and Neurophysiology Department of Physiology Jichi Medical University Shimotsuke‐shi Tochigi‐ken Japan
                [ 2 ] Department of Obesity and Inflammation Research Fukushima Medical University Fukushima‐shi Fukushima‐ken Japan
                Author notes
                [*] [* ] Correspondence

                Masahide Yoshida and Tatsushi Onaka, Division of Brain and Neurophysiology, Department of Physiology, Jichi Medical University, 3311‐1 Yakushiji, Shimotsuke‐shi, Tochigi‐ken 329‐0498, Japan.

                Email: y-masa@ 123456jichi.ac.jp (M.Y.); tonaka@ 123456jichi.ac.jp (T.O.)

                Author information
                https://orcid.org/0000-0001-9921-2211
                https://orcid.org/0000-0001-5666-9035
                Article
                JNE12980
                10.1111/jne.12980
                8243938
                34057769
                df1578e7-b454-46d7-8db2-341993c77109
                © 2021 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 12 March 2021
                : 09 December 2020
                : 16 April 2021
                Page count
                Figures: 11, Tables: 3, Pages: 17, Words: 9896
                Funding
                Funded by: JSPS KAKENHI
                Award ID: 17H04026
                Award ID: 17K19636
                Award ID: 20H03419
                Award ID: 17K08574
                Award ID: 20K07264
                Award ID: 17K08573
                Award ID: 20K07278
                Award ID: 16K08527
                Award ID: 19H05026
                Award ID: 19K06910
                Funded by: Takeda Science Foundation , open-funder-registry 10.13039/100007449;
                Funded by: JMU Graduate Student Start‐Up Grant for Young Investigators
                Funded by: Japan Agency for Medical Research and Development , open-funder-registry 10.13039/100009619;
                Award ID: 18dm0107076h0003
                Categories
                Original Article
                Fundamental and Mechanistic Neuroendocrinology
                Original Article
                Custom metadata
                2.0
                June 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:30.06.2021

                Endocrinology & Diabetes
                affiliative behaviour,allogrooming,social defeat stress,oxytocin
                Endocrinology & Diabetes
                affiliative behaviour, allogrooming, social defeat stress, oxytocin

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