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Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum

Social play is a highly rewarding behavior that is essential for the development of social skills. Social play is impaired in children diagnosed with autism, a disorder with a strong sex bias in prevalence. We recently showed that the arginine vasopressin (AVP) system in the lateral septum (LS) regu...

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Autores principales: Bredewold, Remco, Washington, Catherine, Veenema, Alexa H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081315/
https://www.ncbi.nlm.nih.gov/pubmed/37034639
http://dx.doi.org/10.1101/2023.03.31.535148
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author Bredewold, Remco
Washington, Catherine
Veenema, Alexa H.
author_facet Bredewold, Remco
Washington, Catherine
Veenema, Alexa H.
author_sort Bredewold, Remco
collection PubMed
description Social play is a highly rewarding behavior that is essential for the development of social skills. Social play is impaired in children diagnosed with autism, a disorder with a strong sex bias in prevalence. We recently showed that the arginine vasopressin (AVP) system in the lateral septum (LS) regulates social play behavior sex-specifically in juvenile rats: Administration of a AVP 1a receptor (V1aR) antagonist increased social play behavior in males and decreased it in females. Here, we demonstrate that glutamate, but not GABA, is involved in the sex-specific regulation of social play by the LS-AVP system. First, males show higher extracellular glutamate concentrations in the LS than females while they show similar extracellular GABA concentrations. This resulted in a baseline sex difference in excitatory/inhibitory balance, which was eliminated by V1aR antagonist administration into the LS: V1aR antagonist increased extracellular glutamate release in females but not in males. Second, administration of the glutamate receptor agonist L-glutamic acid into the LS prevented the V1aR antagonist-induced increase in social play behavior in males while mimicking the V1aR antagonist-induced decrease in social play behavior in females. Third, administration of the glutamate receptor antagonists AP-5 and CNQX into the LS prevented the V1aR antagonist-induced decrease in social play behavior in females. Last, both sexes showed increases in extracellular LS-GABA release upon V1aR antagonist administration into the LS and decreases in social play behavior upon administration of the GABA-A receptor agonist muscimol into the LS, suggesting that GABA is not involved in the sex-specific regulation of social play by the LS-AVP system. Finally, to start identifying the cellular mechanism mediating the sex-specific effects of the LS-AVP system on LS-glutamate, we determined the presence of potential sex differences in the type of LS cells expressing V1aR. However, no sex differences were found in the percentage of Avpr1a+ LS cells expressing markers for either GABAergic neurons, somatostatin-expressing neurons, calbindin 1-expressing neurons, or astrocytes. In conclusion, these findings demonstrate that the LS-AVP system regulates social play sex-specifically via differential local glutamatergic neurotransmission in male and female juvenile rats. Further research is required to uncover the underlying cellular mechanism.
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spelling pubmed-100813152023-04-08 Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum Bredewold, Remco Washington, Catherine Veenema, Alexa H. bioRxiv Article Social play is a highly rewarding behavior that is essential for the development of social skills. Social play is impaired in children diagnosed with autism, a disorder with a strong sex bias in prevalence. We recently showed that the arginine vasopressin (AVP) system in the lateral septum (LS) regulates social play behavior sex-specifically in juvenile rats: Administration of a AVP 1a receptor (V1aR) antagonist increased social play behavior in males and decreased it in females. Here, we demonstrate that glutamate, but not GABA, is involved in the sex-specific regulation of social play by the LS-AVP system. First, males show higher extracellular glutamate concentrations in the LS than females while they show similar extracellular GABA concentrations. This resulted in a baseline sex difference in excitatory/inhibitory balance, which was eliminated by V1aR antagonist administration into the LS: V1aR antagonist increased extracellular glutamate release in females but not in males. Second, administration of the glutamate receptor agonist L-glutamic acid into the LS prevented the V1aR antagonist-induced increase in social play behavior in males while mimicking the V1aR antagonist-induced decrease in social play behavior in females. Third, administration of the glutamate receptor antagonists AP-5 and CNQX into the LS prevented the V1aR antagonist-induced decrease in social play behavior in females. Last, both sexes showed increases in extracellular LS-GABA release upon V1aR antagonist administration into the LS and decreases in social play behavior upon administration of the GABA-A receptor agonist muscimol into the LS, suggesting that GABA is not involved in the sex-specific regulation of social play by the LS-AVP system. Finally, to start identifying the cellular mechanism mediating the sex-specific effects of the LS-AVP system on LS-glutamate, we determined the presence of potential sex differences in the type of LS cells expressing V1aR. However, no sex differences were found in the percentage of Avpr1a+ LS cells expressing markers for either GABAergic neurons, somatostatin-expressing neurons, calbindin 1-expressing neurons, or astrocytes. In conclusion, these findings demonstrate that the LS-AVP system regulates social play sex-specifically via differential local glutamatergic neurotransmission in male and female juvenile rats. Further research is required to uncover the underlying cellular mechanism. Cold Spring Harbor Laboratory 2023-03-31 /pmc/articles/PMC10081315/ /pubmed/37034639 http://dx.doi.org/10.1101/2023.03.31.535148 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Bredewold, Remco
Washington, Catherine
Veenema, Alexa H.
Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum
title Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum
title_full Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum
title_fullStr Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum
title_full_unstemmed Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum
title_short Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum
title_sort vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081315/
https://www.ncbi.nlm.nih.gov/pubmed/37034639
http://dx.doi.org/10.1101/2023.03.31.535148
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