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Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence

Social anhedonia, a loss of interest and pleasure in social interactions, is a common symptom of major depression as well as other psychiatric disorders. Depression can occur at any age, but typically emerges in adolescence or early adulthood, which represents a sensitive period for social interacti...

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Autores principales: Lei, Yun, Wang, Dan, Bai, Yu, Nougaisse, Jayvon, Weintraub, Neal L., Guo, Ming, Lu, Xin-Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763124/
https://www.ncbi.nlm.nih.gov/pubmed/36138127
http://dx.doi.org/10.1038/s41380-022-01778-2
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author Lei, Yun
Wang, Dan
Bai, Yu
Nougaisse, Jayvon
Weintraub, Neal L.
Guo, Ming
Lu, Xin-Yun
author_facet Lei, Yun
Wang, Dan
Bai, Yu
Nougaisse, Jayvon
Weintraub, Neal L.
Guo, Ming
Lu, Xin-Yun
author_sort Lei, Yun
collection PubMed
description Social anhedonia, a loss of interest and pleasure in social interactions, is a common symptom of major depression as well as other psychiatric disorders. Depression can occur at any age, but typically emerges in adolescence or early adulthood, which represents a sensitive period for social interaction that is vulnerable to stress. In this study, we evaluated social interaction reward using a conditioned place preference (CPP) paradigm in adolescent male and female mice. Adolescent mice of both sexes exhibited a preference for the social interaction-associated context. Chronic unpredictable stress (CUS) impaired the development of CPP for social interaction, mimicking social anhedonia in depressed adolescents. Conversely, administration of leptin, an adipocyte-derived hormone, enhanced social interaction-induced CPP in non-stressed control mice and reversed social anhedonia in CUS mice. By dissecting the motivational processes of social CPP into social approach and isolation avoidance components, we demonstrated that leptin treatment increased isolation aversion without overt social reward effect. Further mechanistic exploration revealed that leptin stimulated oxytocin gene transcription in the paraventricular nucleus of the hypothalamus, while oxytocin receptor blockade abolished the leptin-induced enhancement of socially-induced CPP. These results establish that chronic unpredictable stress can be used to study social anhedonia in adolescent mice and provide evidence that leptin modulates social motivation possibly via increasing oxytocin synthesis and oxytocin receptor activation.
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spelling pubmed-97631242022-12-21 Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence Lei, Yun Wang, Dan Bai, Yu Nougaisse, Jayvon Weintraub, Neal L. Guo, Ming Lu, Xin-Yun Mol Psychiatry Article Social anhedonia, a loss of interest and pleasure in social interactions, is a common symptom of major depression as well as other psychiatric disorders. Depression can occur at any age, but typically emerges in adolescence or early adulthood, which represents a sensitive period for social interaction that is vulnerable to stress. In this study, we evaluated social interaction reward using a conditioned place preference (CPP) paradigm in adolescent male and female mice. Adolescent mice of both sexes exhibited a preference for the social interaction-associated context. Chronic unpredictable stress (CUS) impaired the development of CPP for social interaction, mimicking social anhedonia in depressed adolescents. Conversely, administration of leptin, an adipocyte-derived hormone, enhanced social interaction-induced CPP in non-stressed control mice and reversed social anhedonia in CUS mice. By dissecting the motivational processes of social CPP into social approach and isolation avoidance components, we demonstrated that leptin treatment increased isolation aversion without overt social reward effect. Further mechanistic exploration revealed that leptin stimulated oxytocin gene transcription in the paraventricular nucleus of the hypothalamus, while oxytocin receptor blockade abolished the leptin-induced enhancement of socially-induced CPP. These results establish that chronic unpredictable stress can be used to study social anhedonia in adolescent mice and provide evidence that leptin modulates social motivation possibly via increasing oxytocin synthesis and oxytocin receptor activation. Nature Publishing Group UK 2022-09-22 2022 /pmc/articles/PMC9763124/ /pubmed/36138127 http://dx.doi.org/10.1038/s41380-022-01778-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lei, Yun
Wang, Dan
Bai, Yu
Nougaisse, Jayvon
Weintraub, Neal L.
Guo, Ming
Lu, Xin-Yun
Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence
title Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence
title_full Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence
title_fullStr Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence
title_full_unstemmed Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence
title_short Leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence
title_sort leptin enhances social motivation and reverses chronic unpredictable stress-induced social anhedonia during adolescence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763124/
https://www.ncbi.nlm.nih.gov/pubmed/36138127
http://dx.doi.org/10.1038/s41380-022-01778-2
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